prospero is expressed in neuronal precursors and encodes a nuclear protein that is involved in the control of axonal outgrowth in Drosophila.

Neurogenesis in Drosophila begins with the formation of neuronal precursors, which give rise to neurons of individual identity. To find out whether there are genes that are expressed in most or all neuronal precursors and are involved in controlling particular aspects of neuronal differentiation, we used the enhancer-trap method to screen for such "neuronal precursor genes." One gene of this group is prospero. Our mutant analysis indicates that prospero regulates other neuronal precursor genes and is essential for the axonal outgrowth and pathfinding of numerous central and peripheral neurons. prospero encodes a large nuclear protein with multiple homopolymeric amino acid stretches and is expressed in neuronal precursors early during their formation. It is probably generally required for proper neuronal differentiation.     

Morphological characteristics of hippocampal neurons developing in cell cultures

Using observation of living cells and neurohistological methods, we have investigated growth dynamics, fasciculation of fibers and morphogenesis of neurons in hippocampal cell cultures of 18-19-day-old mouse embryos. The development of the system of neuronal outgrowths with predominant growth of apical dendrite started on the 4th-6th day of cultivation and resulted in the formation of pyramidal neurons possessing the main morphological signs of pyramidal hippocampal neurons developing in situ. Thus, the morphogenetic programme of dendrite development can ensure the in vitro formation of neurons of a certain morphological phenotype. One of the possible prerequisites of the programme realization appears to be the inductive influence of afferent nervous fibers which reach hippocampal neurons in situ in the pre-cultivation period.     

The homeodomain factor lbx1 distinguishes two major programs of neuronal differentiation in the dorsal spinal cord

Dorsal horn neurons in the spinal cord integrate and relay sensory information. Here, we show that the expression of the homeobox gene Lbx1 distinguishes two major neuronal classes generated in the dorsal spinal cord. The Lbx1(-) (class A) and Lbx1(+) (class B) neurons differ in their dependence on roof plate BMP signals for specification and settle in the deep and superficial dorsal horn, respectively. Lbx1 misexpression blocks the differentiation of class A neurons. Conversely, in Lbx1 mutant mice, class B neurons assume the identity of class A neurons. As a consequence, the morphology and neuronal circuitry of the dorsal horn are aberrant. We conclude that Lbx1 distinguishes two major neuronal classes in the dorsal spinal cord and is an important determinant of their distinct differentiation programs.     

Ubiquitination of the GTPase Rap1B by the ubiquitin ligase Smurf2 is required for the establishment of neuronal polarity

The development of a polarised morphology with multiple dendrites and a single axon is an essential step in the differentiation of neurons. The establishment of neuronal polarity is directed by the sequential activity of the GTPases Rap1B and Cdc42. Rap1B is initially present in all neurites of unpolarised neurons, but becomes restricted to the tip of a single process during the establishment of neuronal polarity where it specifies axonal identity. Here, we show that the ubiquitin ligases Smad ubiquitination regulatory factor-1 (Smurf1) and Smurf2 are essential for neurite growth and neuronal polarity, respectively, and regulate the GTPases Rho and Rap1B in hippocampal neurons. Smurf2 is required for the restriction of Rap1B to a single neurite. Smurf2 ubiquitinates inactive Rap1B and initiates its degradation through the ubiquitin/proteasome pathway (UPS). Degradation of Rap1B restricts it to a single neurite and thereby ensures that neurons extend a single axon.     

Notch resolves mixed neural identities in the zebrafish epiphysis

Manipulation of Notch activity alters neuronal subtype identity in vertebrate neuronal lineages. Nonetheless, it remains controversial whether Notch activity diversifies cell fate by regulating the timing of neurogenesis or acts directly in neuronal subtype specification. Here, we address the role of Notch in the zebrafish epiphysis, a simple structure containing only two neural subtypes: projection neurons and photoreceptors. Reducing the activity of the Notch pathway results in an excess of projection neurons at the expense of photoreceptors, as well as an increase in cells retaining a mixed identity. However, although forced activation of the pathway inhibits the projection neuron fate, it does not promote photoreceptor identity. As birthdating experiments show that projection neurons and photoreceptors are born simultaneously, Notch acts directly during neuronal specification rather than by controlling the timing of neurogenesis. Finally, our data suggest that two distinct signals are required for photoreceptor fate specification: one for the induction of the photoreceptor fate and the other, involving Notch, for the inhibition of projection neuron traits. We propose a novel model in which Notch resolves mixed neural identities by repressing an undesired genetic program.