No abstract

FGF acts as a positional cue that prevents premature neural crest cell specification and EMT caudally while, at the same time, retinoic acid promotes EMT rostrally.

Members of the Sox family of transcription factors are involved in a number of crucial developmental processes, including sex determination, neurogenesis and skeletal development. LSox5 is a member of the group D Sox factors that,in conjunction with Sox6 and Sox9, promotes chondrogenesis by activating the expression of cartilage-specific extracellular matrix molecules. We have cloned the chicken homologue of LSox5 and found that it is initially expressed in the premigratory and migratory neural crest after Slugand FoxD3. Subsequently, the expression of LSox5 is maintained in cephalic crest derivatives, and it appears to be required for the development of the glial lineage, the Schwann cells and satellite glia in cranial ganglia. Misexpression of LSox5 in the cephalic neural tube activated RhoB expression throughout the dorsoventral axis. Furthermore, the prolonged forced expression of LSox5 enlarged the dorsal territory in which the neural crest is generated, extended the `temporal window' of neural crest segregation, and led to an overproduction of neural crest cells in cephalic regions. In addition to HNK-1, the additional neural crest cells expressed putative upstream markers (Slug, FoxD3) indicating that a regulatory feedback mechanism may operate during neural crest generation. Thus, our data show that in addition to the SoxE genes(Sox9 and Sox10) a SoxD gene (Sox5) also participates in neural crest development and that a cooperative interaction may operate during neural crest generation, as seen during the formation of cartilage.

Genes of the SOX family of high-mobility group transcription factors are essential during nervous system development. In this study, we show that SOX5 is expressed by neural progenitors in the chick spinal cord and is turned off as differentiation proceeds. The overexpression of SOX5 in neural progenitors causes premature cell cycle exit and prevents terminal differentiation. Conversely, knocking down SOX5 protein extends the proliferative period of neural progenitors and causes marked cell death in a dorsal interneuron (dI3) population. Furthermore, SOX5 reduces WNT-b-catenin signalling, thereby triggering the expression of the negative regulator of the pathway axin2. We propose that SOX5 regulates the timing of cell cycle exit by opposing WNT-b-catenin activity on cell cycle progression.