A neural crest deficit in Down syndrome mice is associated with deficient mitotic response to Sonic hedgehog |
| |
| Authors: | Randall J. Roper Justin F. VanHorn Colyn C. Cain Roger H. Reeves |
| |
| Affiliation: | 1. Department of Physiology and McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Biophysics 201, 725 North Wolfe Street, Baltimore, MD 21205, USA;2. Department of Biology and Indiana University Center for Regenerative Biology and Medicine, Indiana University-Purdue University Indianapolis, 723 W. Michigan Street, SL 306, Indianapolis, IN 46202, USA;3. Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA |
| |
| Abstract: | Trisomy 21 results in phenotypes collectively referred to as Down syndrome (DS) including characteristic facial dysmorphology. Ts65Dn mice are trisomic for orthologs of about half of the genes found on human chromosome 21 and exhibit DS-like craniofacial abnormalities, including a small dysmorphic mandible. Quantitative analysis of neural crest (NC) progenitors of the mandible revealed a paucity of NC and a smaller first pharyngeal arch (PA1) in Ts65Dn as compared to euploid embryos. Similar effects in PA2 suggest that trisomy causes a neurocristopathy in Ts65Dn mice (and by extension, DS). Further analyses demonstrated deficits in delamination, migration, and mitosis of trisomic NC. Addition of Sonic hedgehog (Shh) growth factor to trisomic cells from PA1 increased cell number to the same level as untreated control cells. Combined with previous demonstrations of a deficit in mitogenic response to Shh by trisomic cerebellar granule cell precursors, these results implicate common cellular and molecular bases of multiple DS phenotypes. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
