Homeobox gene hoxa3 is essential for the formation of the carotid body in the mouse embryos

Homeobox gene Hoxa3 is strongly expressed in the third pharyngeal arch and pouch. We found that Hoxa3 homozygous null mutant mice had the lack of the carotid body. In all late-term mutant embryos examined (n = 10), no carotid body was present. The carotid body rudiment is formed in the wall of the third branchial artery, which develops into the common carotid artery and the first part of the internal carotid artery. The symmetrical patterns of the third, fourth, and sixth arch arteries were observed in wild-type littermates at embryonic day (E) 10.5-12.5. In Hoxa3 homozygous mutant embryos, however, the third arch artery began to degenerate at E10.5 and almost disappeared at E11.5. Furthermore, the bifurcation of the common carotid artery at the normal position, i.e., at the upper end of the larynx, was never detected in the mutant embryos at E16.5-E18.5. The common carotid artery of the homozygous mutants was separated into the internal and external carotid arteries immediately after its origin. Thus, the present study evidenced that the absence of the carotid body in Hoxa3 homozygous mutants is due to the defect of development of the third arch artery, resulting in malformation of the carotid artery system. During fetal development, the carotid body of mice is in close association with the superior cervical ganglion of the sympathetic trunk. The superior cervical ganglion rather showed hypertrophic features in Hoxa3 homozygous mutants lacking the carotid body.     

<Emphasis Type="Italic">Hoxa3</Emphasis> regulates the proliferation and differentiation of the third pharyngeal arch mesenchyme in mice

Genetic disruption of Hoxa3 results in bilateral defects of the common carotid artery, which is derived from the third branchial arch artery. The tunica media of the great arteries derived from the arch arteries is formed by the ectomesenchymal neural crest cells. To examine the etiology of the regression of the third arch artery, we generated Hoxa3 homozygous null mutant embryos that expressed a lacZ marker transgene driven by a connexin43 (Cx43): promoter in the neural crest cells. The expression of -galactosidase in these mouse embryos was examined by both whole-mount X-gal staining and immunohistochemistry with the monoclonal -galactosidase antibody on sections. The migration of neural crest cells from the neural tube to the third branchial arch was not affected in the Hoxa3 homozygotes. The initial formation of the third arch artery was also not disturbed. The artery, however, regressed at embryonic day 11.5 (E11.5), when differentiation of the third pharyngeal arch began. The internal and external carotid arteries arose from the dorsal aorta in E12.5 null mutants, which showed an abnormal persistence of the ductus caroticus. The third pharyngeal arch of wild-type mice fuses with the fourth and second arches at E12.0. In the Hoxa3 null mutants, however, the fusion was delayed, and the hypoplastic third pharyngeal arch was still discerned at E12.5. Moreover, the number of proliferating cells in the third arch of the null mutants was small compared with that in the wild-type. Thus, Hoxa3 is required for the growth and differentiation of the third pharyngeal arch. The defective development of the third pharyngeal arch may induce the anomalies of the carotid artery system. This work was supported in part by a grant (no. 14570026) from the Ministry of Education of Japan to Y.K.     

<Emphasis Type="Italic">Hoxa3</Emphasis> and signaling molecules involved in aortic arch patterning and remodeling

Anomalies of the aortic arch have long been of anatomicoclinical interest. Recent studies on gene-targeted mice have identified the candidate genes that are involved in the patterning and remodeling of the pharyngeal arch arteries. In this review, we discuss our present knowledge with regard to the signaling molecules that regulate specific aspects of arch artery development. We focus first on Hoxa3, because it plays a critical role in the regulation of the differentiation of the third pharyngeal arch. Hoxa3 is expressed by the neural crest cells that originate from the rhombomeres, viz., (r)5, r6, and r7, and populate the third pharyngeal arch; it is also expressed in the third pharyngeal pouch. In Hoxa3 homozygous null mutant mice, the third arch artery degenerates bilaterally at embryonic day 11.5, resulting in the malformation of the carotid artery system. Complex combinatorial signals among the neural crest cells, pharyngeal mesoderm, ectoderm, and pouch endoderm are required for the proper development of the arch arterial system. Therefore, we highlight the numerous signaling pathways and individual genes expressed by the ectomesenchymal neural crest cells and also by the other epithelial and mesodermal cells of the pharynx. Defects in these genes result in malformations of the arch artery derivatives. This review should deepen our understanding of congenital human syndromes with abnormal patterns of pharyngeal arch arteries.     

Loss of Eph-receptor expression correlates with loss of cell adhesion and chondrogenic capacity in Hoxa13 mutant limbs.

Mesenchymal patterning is an active process whereby genetic commands coordinate cell adhesion, sorting and condensation, and thereby direct the formation of morphological structures. In mice that lack the Hoxa13 gene, the mesenchymal condensations that form the autopod skeletal elements are poorly resolved, resulting in missing digit, carpal and tarsal elements. In addition, mesenchymal and endothelial cell layers of the umbilical arteries (UAs) are disorganized, resulting in their stenosis and in embryonic death. To further investigate the role of Hoxa13 in these phenotypes, we generated a loss-of-function allele in which the GFP gene was targeted into the Hoxa13 locus. This allele allowed FACS isolation of mesenchymal cells from Hoxa13 heterozygous and mutant homozygous limb buds. Hoxa13(GFP) expressing mesenchymal cells from Hoxa13 mutant homozygous embryos are defective in forming chondrogenic condensations in vitro. Analysis of pro-adhesion molecules in the autopod of Hoxa13 mutants revealed a marked reduction in EphA7 expression in affected digits, as well as in micromass cell cultures prepared from mutant mesenchymal cells. Finally, antibody blocking of the EphA7 extracellular domain severely inhibits the capacity of Hoxa13(GFP) heterozygous cells to condense and form chondrogenic nodules in vitro, which is consistent with the hypothesis that reduction in EphA7 expression affects the capacity of Hoxa13(-/-) mesenchymal cells to form chondrogenic condensations in vivo and in vitro. EphA7 and EphA4 expression were also decreased in the mesenchymal and endothelial cells that form the umbilical arteries in Hoxa13 mutant homozygous embryos. These results suggest that an important role for Hoxa13 during limb and UA development is to regulate genes whose products are required for mesenchymal cell adhesion, sorting and boundary formation.     

Mash1 is required for glomus cell formation in the mouse carotid body

The carotid body consists of chemoreceptive glomus cells, sustentacular cells and nerve endings. The murine carotid body, located at the carotid bifurcation, is always joined to the superior cervical ganglion of the sympathetic trunk. Glomus cells and sympathetic neurons are immunoreactive for the TuJ1, PGP9.5, tyrosine hydroxylase (TH) and neuropeptide Y (NPY) markers. Glomus cells are also immunoreactive for serotonin (5-HT). A targeted mutation of Mash1, a mouse homolog of the Drosophila achaete-scute complex, results in the elimination of sympathetic ganglia. In Mash1 null mutant mice, the carotid body primordium forms normally in the wall of the third arch artery at embryonic day (E) 13.0 and continues to develop, although the superior cervical ganglion is completely absent. However, no cells in the mutant carotid body display the TuJ1, PGP 9.5, TH, NPY and 5-HT markers throughout development. The absence of glomus cells was also confirmed by electron microscopy. The carotid body of newborn null mutants is composed of mesenchymal-like cells and nerve fibers. Many cells immunoreactive for the S-100 protein, a sustentacular cell marker, appear in the mutant carotid body during fetal development. The Mash1 gene is thus required for the genesis of glomus cells but not for sustentacular cells.     

FRS2 alpha 2F/2F mice lack carotid body and exhibit abnormalities of the superior cervical sympathetic ganglion and carotid sinus nerve

The docking protein FRS2α is an important mediator of fibroblast growth factor (FGF)-induced signal transduction, and functions by linking FGF receptors (FGFRs) to a variety of intracellular signaling pathways. We show that the carotid body is absent in FRS2α^2F/2F mice, in which the Shp2-binding sites of FRS2α are disrupted. We also show that the carotid body rudiment is not formed in the wall of the third arch artery in mutant embryos. In wild-type mice, the superior cervical ganglion of the sympathetic trunk connects to the carotid body in the carotid bifurcation region, and extends thick nerve bundles into the carotid body. In FRS2α^2F/2F mice, the superior cervical ganglion was present in the lower cervical region as an elongated feature, but failed to undergo cranio-ventral migration. In addition, few neuronal processes extended from the ganglion into the carotid bifurcation region. The number of carotid sinus nerve fibers that reached the carotid bifurcation region was markedly decreased, and baroreceptor fibers belonging to the glossopharyngeal nerve were absent from the basal part of the internal carotid artery in FRS2α^2F/2F mutant mice. In some of the mutant mice (5 out of 14), baroreceptors and some glomus cells were distributed in the wall of the common carotid artery, onto which the sympathetic ganglion abutted. We propose that the sympathetic ganglion provides glomus cell precursors into the third arch artery derivative in the presence of sensory fibers of the glossopharyngeal nerve.     

The role of Hoxa3 gene in parathyroid gland organogenesis of the mouse.

Mice with a targeted deletion of the Hoxa3 gene have defects of derivatives of the third branchial arch and pouch. To address the role of the Hoxa3 gene in parathyroid organogenesis, we examined the third pharyngeal pouch development by immunohistochemistry (IHC) using the secretory protein (SP)-1/chromogranin A antiserum, which recognizes the parathyroid from its initial formation onward. At embryonic day (E) 11.5, the SP-1/chromogranin A-immunoreactive primary rudiment of the parathyroid appeared in the cranial region of the third pharyngeal pouch of wild-type embryos. In Hoxa3-null mutants, the third pharyngeal pouch was normally formed but failed to differentiate into the parathyroid rudiment, showing no immunoreactivity for SP-1/chromogranin A. Classic studies using chick-quail chimeras have demonstrated that the ectomesenchymal neural crest cells are required for proper development of the pharyngeal pouch-derived organs, including the thymus and parathyroid glands. To visualize the migration and development of mesenchymal neural crest cells in Hoxa3 mutants, the heterozygotes were crossed with connexin43-lacZ transgenic mice in which beta-galactosidase expression was specific to the neural crest cells. In Hoxa3 homozygotes and in wild types, ectomesenchymal neural crest cells densely populated the pharyngeal arches, including the third one, and surrounded the third pouch epithelium. These results indicate that lack of the Hoxa3 gene affects the intrinsic ability of the third pharyngeal pouch to form the parathyroid rudiment and has no detectable effect on the migration of neural crest cells.     

Abnormalities of caudal pharyngeal pouch development in Pbx1 knockout mice mimic loss of Hox3 paralogs

Pbx1 is a TALE-class homeodomain protein that functions in part as a cofactor for Hox class homeodomain proteins. Previous analysis of the in vivo functions of Pbx1 by targeted mutagenesis in mice has revealed roles for this gene in skeletal patterning and development and in the organogenesis of multiple systems. Both RNA expression and protein localization studies have suggested a possible role for Pbx1 in pharyngeal region development. As several Hox mutants have distinct phenotypes in this region, we investigated the potential requirement for Pbx1 in the development of the pharyngeal arches and pouches and their organ derivatives. Pbx1 homozygous mutants exhibited delayed or absent formation of the caudal pharyngeal pouches, and disorganized patterning of the third pharyngeal pouch. Formation of the third pouch-derived thymus/parathyroid primordia was also affected, with absent or hypoplastic primordia, delayed expression of organ-specific differentiation markers, and reduced proliferation of thymic epithelium. The fourth pouch and the fourth pouch-derived ultimobranchial bodies were usually absent. These phenotypes are similar to those previously reported in Hoxa3(-/-) single mutants and Hoxa1(-/-);Hoxb1(-/-) or Hoxa3(+/-);Hoxb3(-/-);Hoxd3(-/-) compound mutants, suggesting that Pbx1 acts together with multiple Hox proteins in the development of the caudal pharyngeal region. However, some aspects of the Pbx1 mutant phenotype included specific defects that were less severe than those found in known Hox mutant mice, suggesting that some functions of Hox proteins in this region are Pbx1-independent.     

Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development.

The analysis of mice mutant for both Hoxa1 and Hoxb1 suggests that these two genes function together to pattern the hindbrain. Separately, mutations in Hoxa1 and Hoxb1 have profoundly different effects on hindbrain development. Hoxa1 mutations disrupt the rhombomeric organization of the hindbrain, whereas Hoxb1 mutations do not alter the rhombomeric pattern, but instead influence the fate of cells originating in rhombomere 4. We suggest that these differences are not the consequences of different functional roles for these gene products, but rather reflect differences in the kinetics of Hoxa1 and Hoxb1 gene expression. In strong support of the idea that Hoxa1 and Hoxb1 have overlapping functions, Hoxa1/Hoxb1 double mutant homozygotes exhibit a plethora of defects either not seen, or seen only in a very mild form, in mice mutant for only Hoxa1 or Hoxb1. Examples include: the loss of both rhombomeres 4 and 5, the selective loss of the 2(nd) branchial arch, and the loss of most, but not all, 2(nd) branchial arch-derived tissues. We suggest that the early role for both of these genes in hindbrain development is specification of rhombomere identities and that the aberrant development of the hindbrain in Hoxa1/Hoxb1 double mutants proceeds through two phases, the misspecification of rhombomeres within the hindbrain, followed subsequently by size regulation of the misspecified hindbrain through induction of apoptosis.     

Hoxa11 and Hoxd11 regulate branching morphogenesis of the ureteric bud in the developing kidney

Hoxa11 and Hoxd11 are functionally redundant during kidney development. Mice with homozygous null mutation of either gene have normal kidneys, but double mutants have rudimentary, or in extreme cases, absent kidneys. We have examined the mechanism for renal growth failure in this mouse model and find defects in ureteric bud branching morphogenesis. The ureteric buds are either unbranched or have an atypical pattern characterized by lack of terminal branches in the midventral renal cortex. The mutant embryos show that Hoxa11 and Hoxd11 control development of a dorsoventral renal axis. By immunohistochemical analysis, Hoxa11 expression is restricted to the early metanephric mesenchyme, which induces ureteric bud formation and branching. It is not found in the ureteric bud. This suggests that the branching defect had been caused by failure of mesenchyme to epithelium signaling. In situ hybridizations with Wnt7b, a marker of the metanephric kidney, show that the branching defect was not simply the result of homeotic transformation of metanephros to mesonephros. Absent Bf2 and Gdnf expression in the midventral mesenchyme, findings that could by themselves account for branching defects, shows that Hoxa11 and Hoxd11 are necessary for normal gene expression in the ventral mesenchyme. Attenuation of normal gene expression along with the absence of a detectable proliferative or apoptotic change in the mutants show that one function of Hoxa11 and Hoxd11 in the developing renal mesenchyme is to regulate differentiation necessary for mesenchymal-epithelial reciprocal inductive interactions.     

Suppression of polydactyly of the Gli3 mutant (extra toes) by deltaEF1 homozygous mutation

Digit patterning is established through multiple genetic interactions. Delta-crystallin enhancer/E2-box factor (deltaEF1) is a zinc finger and homeodomain containing repressor protein, and is expressed in the posterior half of the forelimb bud and in the entire hindlimb bud during the early stage of limb development. The 6EF1-deficient mutant mice display various skeletal abnormalities, among which inferior ossification and abnormal patterning of autopodial bones are similar to those observed in Hox and Gli gene mutants. Gli3 mutant mice, extra toes (Xt), exhibit pre-axial polydactyly losing the identity of digit I. It is demonstrated here that deltaEF1null(lacZ) homozygosity suppressed formation of the extra digit, uniquely of the hindlimb, in both Gli3XtJ heterozygous and homozygous mutants, but with no restoration of digit I identity. In Gli3XtJ mutants, the Hoxd13 expression domain was expanded more dramatically in homozygotes. In Gli3XtJ;deltaEF1null(lacZ) double homozygous mutants, Hoxd13 expression once expanded in Gli3XtJ homozygous mutant was reduced, more conspicuously in the hindlimbs, which may account for hindlimb-restricted suppression of formation of the extra digit. The data suggest the possibility that the extent of Hoxd13 expression along the distal margin of the limb bud is determinative in defining the digit number.     

Altered Hox expression and increased cell death distinguish Hypodactyly from Hoxa13 null mice.

Hypodactyly (Hoxa13Hd) mice have a small deletion within the coding sequence of Hoxa13 and a limb phenotype that is more severe than that of mice with an engineered null allele of Hoxa13. We used whole-mount in situ hybridization, Nile blue sulfate staining and genetic crosses to determine the basis for the phenotypic differences between these two mutants. Expression of Hoxd13 was unaffected in Hoxa13-/- mice, but its domain was reduced at the anterior and posterior margins of the autopod in Hoxa13Hd/Hd limb buds. The maturation of Hoxd11 expression was delayed and expression of Hoxa11 failed to become restricted to the autopod/zeugopod junction in both Hoxa13Hd/Hd and Hoxa13-/- limb buds compared to wild-type mice. Fgf8 expression was normal in both Hoxa13Hd/Hd and Hoxa13-/- mice throughout limb development. A dramatic increase in cell death was observed in limb bud mesenchyme of Hoxa13Hd/Hd mice as early as E11.5 but not in mice homozygous for the null allele. Genetic background was excluded as the basisforthe phenotypic differences. Compound heterozygotes (Hoxa13-/Hd) displayed an intermediate phenotype relative to both homozygotes suggesting that Hoxa13Hd has an effect on the development of the autopod beyond that which may result from a loss of HOXA13 protein. These results showthat Hoxa13Hd has a negative effect on the survival of the mesenchyme in the autopod, unlike the Hoxa13 null mutation, that cannot be explained by a failure of the AER to express Fgfs. In addition, at least one target of HOXA13 may be Hoxa11.     

Vascular corrosion replicas of chemo-baroreceptors in fish: The carotid labyrinth in Ictaluridae and Clariidae

Summary Scanning electron microscopy of vascular corrosion replicas and light microscopy revealed a pair of highly vascularized tissues, the carotid labyrinths, in the dorsal head region of the channel catfish, Ictalurus punctatus, the black bullhead, I. melas, and the walking catfish, Clarias batrachus. The labyrinth consists of a myriad of arterioles that arise from the common carotid artery immediately distal to the origin of the common carotid from the efferent branchial (epibranchial) artery of the first gill arch. The arterioles anastomose with each other to form: (1) the internal carotid artery which supplies the brain, and (2) several anteriolateral arteries that extend into the anterior head. In the ictalurids the common carotid artery emerges from the labyrinth intact and continues anteriorly as the large olfactory artery, whereas in Clarias all postlabyrinthine vessels result from arborization of the common carotid and subsequent anastomosis of the arterioles. Similarities between piscine and amphibian carotid labyrinths and the anatomical proximity of the former with the gills suggest that, in Ictaluridae, the labyrinth has a chemoor baroreceptor function.Supported by NSF Grant No. PCM 79-23073The authors wish to thank K. Drajus, D. Kullman, E. Boland and Dr. J. O'Malley for their most capable help. The authors also express their gratitude to P. Shafland and the Florida Game and Fresh Water Fish Commission for providing Clarias     

Expression of neuropeptide Y and agouti-related peptide in the hypothalamic arcuate nucleus of newborn neurogenin3 null mutant mice

Mice deficient in neurogenin 3 (Ngn3) fail to generate pancreatic endocrine cells and intestinal endocrine cells. Hypothalamic neuropeptides implicated in the control of energy homeostasis might also be affected in Ngn3 homozygous null mutant mice. We investigated the expression of two prominent orexigenic neuropeptides, neuropeptide Y (NPY) and agouti-related protein (AgRP), in the hypothalamic arcuate nucleus of newborn wild-type and Ngn3 null mutant mice. Immunohistochemical analysis demonstrated that, in Ngn3 null mutants, the number of NPY-immunoreactive neurons and nerve fibers was markedly increased in the arcuate nucleus, and the nerve fibers were widely distributed in the hypothalamic area, including the paraventricular and dorsomedial nuclei. Little increase of AgRP immunoreactivity was detected in the arcuate nucleus of mutant mice. In situ hybridization analysis confirmed the increased population of the NPY neurons in the arcuate nucleus of the mutants. The NPY mRNA level, as estimated by laser capture microdissection and real-time quantitative polymerase chain reaction, was 371% higher in Ngn3 null mutants than in wild-type mice. AgRP mRNA levels did not differ significantly between the null mutants and wild-type mice. Thus, up-regulation of the hypothalamic NPY system is probably a feature characteristic of Ngn3 null mice.     

Deletion of peptide amidation enzymatic activity leads to edema and embryonic lethality in the mouse

Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the COOH-terminal amidation of peptide hormones. We previously had found high expression of PAM in several regions of the developing rodent. To determine the function of PAM during mouse embryogenesis, we produced a null mutant of the PAM gene. Homozygous mutants die in utero between e14.5 and e15.5 with severe edema that is likely due to cardiovascular deficits. These defects include thinning of the aorta and carotid arteries and are very similar to those of the recently characterized adrenomedullin (AM) gene KO despite the presence of elevated immunoreactive AM in PAM KO embryos. No peptide amidation activity was detected in PAM mutant embryos, and there was no moderation of the AM-like phenotype that could be expected if any alternative peptide amidation mechanism exists in the mouse. Despite the proposed contribution of amidated peptides to neuronal cell proliferation, no alteration in neuroblast proliferation was observed in homozygous mutant embryos prior to lethality. Mice heterozygous for the mutant PAM allele develop normally and express wildtype levels of several amidated peptides despite having one half the wildtype levels of PAM activity and PAM protein. Nonetheless, both an increase in adiposity and a mild glucose intolerance developed in aged (>10 months) heterozygous mice compared to littermate controls. Ablation of PAM thus demonstrates an essential function for this gene during mouse development, while alterations in PAM activity in the adult may underlie more subtle physiologic effects.     

Hoxa3 and pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis

The thymus and parathyroid glands in mice develop from a thymus/parathyroid primordium that forms from the endoderm of the third pharyngeal pouch. We investigated the molecular mechanisms that promote this unique process in which two distinct organs form from a single primordium, using mice mutant for Hoxa3 and Pax1. Thymic ectopia in Hoxa3(+/-)Pax1(-/-) compound mutants is due to delayed separation of the thymus/parathyroid primordium from the pharynx. The primordium is hypoplastic at its formation, and has increased levels of apoptosis. The developing third pouch in Hoxa3(+/-)Pax1(-/-) compound mutants initiates normal expression of the parathyroid-specific Gcm2 and thymus-specific Foxn1 genes. However, Gcm2 expression is reduced at E11.5 in Pax1(-/-) single mutants, and further reduced or absent in Hoxa3(+/-)Pax1(-/-) compound mutants. Subsequent to organ-specific differentiation from the shared primordium, both the parathyroids and thymus developed defects. Parathyroids in compound mutants were smaller at their formation, and absent at later stages. Parathyroids were also reduced in Pax1(-/-) mutants, revealing a new function for Pax1 in parathyroid organogenesis. Thymic hypoplasia at later fetal stages in compound mutants was associated with increased death and decreased proliferation of thymic epithelial cells. Our results suggest that a Hoxa3-Pax1 genetic pathway is required for both epithelial cell growth and differentiation throughout thymus and parathyroid organogenesis.     

Unloading arterial baroreceptors causes neurogenic hypertension

We developed a new model to examine the role of arterial baroreceptors in the long-term control of mean arterial pressure (MAP) in dogs. Baroreceptors in the aortic arch and one carotid sinus were denervated, and catheters were implanted in the descending aorta and common carotid arteries. MAP and carotid sinus pressure (CSP) averaged 104 +/- 2 and 102 +/- 2 mmHg (means +/- 1 SE), respectively, during a 5-day control period. Baroreceptor unloading was induced by ligation of the common carotid artery proximal to the innervated sinus (n = 6 dogs). MAP and CSP averaged 127 +/- 7 and 100 +/- 3 mmHg, respectively, during the 7-day period of baroreceptor unloading. MAP was significantly elevated (P < 0.01) compared to control, but CSP was unchanged. Heart rate and plasma renin activity increased significantly in response to baroreceptor unloading. Removal of the ligature to restore normal flow through the carotid resulted in normalization of all variables. Ligation of the carotid below a denervated sinus (n = 4) caused a significant decrease in CSP but no systemic hypertension. These results indicate that chronic unloading of carotid baroreceptors can produce neurogenic hypertension and provide strong evidence that arterial baroreceptors are involved in the long-term control of blood pressure.     

Observations on the structure and innervation of the carotid sinus complex in the African porcupine (Hystrix cristata)

The carotid arterial system of the porcupine Hysitrix cristota has been studied using light and electron microscopy. Emphasis has been placed on describing the structure and innervation of the carotid sinus area located at the origin of the internal carotid artery. The sinus wall has a largely elastic structure and a reduced smooth muscle content. A functional relationship is proposed between the elastic structure of the sinus wall and baroreceptor mechanisms.     

叉头框-c2基因在主动脉弓发育过程中的作用

为了研究叉头框-c2（Forkhead Box c2, Fox c2）基因在心血管发生和发育中的作用, 通过制作小鼠的Fox c2 基因无效突变,解析该基因缺失鼠主动脉弓的异常发育状况.纯合子胎鼠从12.5天胚胎(embryo, E)开始有宫内死亡;即使完成宫内发育过程,新生鼠出生24 h后也全部死亡.这些鼠全部表现出与人的先天性心血管发育缺陷相似的B型或C型主动脉弓离断.杂合子鼠发育正常.E10.5胚胎的原位杂交分析显示,Fox c2 mRNA在第三、第四和第六弓型动脉强烈表达,而第四弓型动脉在E10.5胚胎后逐渐消失.这些结果表明,在主动脉弓形成过程中,Fox c2基因产物是左第四弓形动脉广泛改建所必需.