Crossregulation between Neurogenin2 and pathways specifying neuronal identity in the spinal cord.
We have examined how genetic pathways that specify neuronal identity and regulate neurogenesis interface in the vertebrate neural tube. Here, we demonstrate that expression of the proneural gene Neurogenin2 (Ngn2) in the ventral spinal cord results from the modular activity of three enhancers active in distinct progenitor domains, suggesting that Ngn2 expression is controlled by dorsoventral patterning signals. Consistent with this hypothesis, Ngn2 enhancer activity is dependent on the function of Pax6, a homeodomain factor involved in specifying the identity of ventral spinal cord progenitors. Moreover, we show that Ngn2 is required for the correct expression of Pax6 and several homeodomain proteins expressed in defined neuronal populations. Thus, neuronal differentiation involves crossregulatory interactions between a bHLH-driven program of neurogenesis and genetic pathways specifying progenitor and neuronal identity in the spinal cord.
Scardigli
R
R
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, B.P. 163, 67404 Illkirch Cédex, C.U., de Strasbourg, France.
Schuurmans
C
C
Gradwohl
G
G
Guillemot
F
F
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D004742:Enhancer Elements, Genetic; D005136:Eye Proteins; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000166:cytology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology*; D013234:Stem Cells / Q000166:cytology; D001616:beta-Galactosidase / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D001616:beta-Galactosidase; C491183:NEUROG2 protein, human; C102938:Neurog2 protein, mouse; C000605730:PAX6 protein, human; C000605732:Pax6 protein, mouse