Developmental and Signaling Pathways: Neuroblast Temporal Transitions in the Embryonic CNS
Brody, T. and Odenwald, W. F. (2002). Cellular diversity in the developing nervous system: a temporal view from Drosophila. Development 129: 3763-3770. PubMed ID: 12135915

Legend: Sequential transitions in neuroblast gene expression generate layered sublineage expression domains. During each temporal gene expression window, asymmetric NB divisions give rise to GMCs that are marked by the continued presence of the temporal factor that is expressed in the NB during its birth. These transcription factors are also detected in nascent postmitotic neurons and glia. Cells that express Hunchback (Hb) are positioned on the inner basal surface of the developing ganglion, and are pushed deeper into the developing neuromere upon the birth of subsequent lineage marked by expression of Kruppel (Kr), Pdm-1 (Nubbin) and Pdm-2, Castor (Cas), and Grainyhead (Grh). As a consequence of these transitions in NB gene expression during lineage development, layered transcription factor expression domains are formed throughout the developing CNS. The temporal factors may act as competence factors, determining the ability of the NB to generate progeny with distinct differentiative states (Brody and Odenwald, 2002).

Molecular evidence for the temporal diversification of Drosophila NB progeny comes from studies of the zinc-finger transcription factor Castor (Cas). An analysis of Cas transcriptional regulatory targets revealed that the DNA-binding specificity of Cas is similar if not identical to that of another structurally different zinc-finger protein known as Hunchback (Hb). Previous work examining Hb transcriptional targets identified two genes encoding the functionally redundant POU domain transcription factors, pdm-1 and pdm-2, referred to here as pdm. In the cellular blastoderm, Hb is a repressor of pdm expression. It was reasoned that Hb might target pdm during neurogenesis, and as Cas binds to Hb consensus binding sites, perhaps Cas too regulates pdm during neurogenesis. Subsequent studies have shown that Hb and Cas act early and late, respectively, to restrict pdm expression to a subset of neural cells that maintain an intermediate position sandwiched between early-born neural progeny expressing Hb and late-born neural progeny expressing Cas. Additional lineage marking studies and in vitro culture studies have revealed that these layered expression domains are formed by transitions in NB gene expression, and that the GMC and neural progeny maintain expression of the transcription factor active in the NB during each temporal window. Taken together, these studies indicate that many NBs undergo sequential changes in their gene expression profiles during lineage development (Brody and Odenwald, 2002).

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