Programmed Transformations in Neuroblast Gene Expression during Drosophila CNS Lineage Development

Abstract

During Drosophila embryonic CNS development, the sequential neuroblast (NB) expression of four proteins, Hunchback (Hb), Pou-homeodomain proteins 1 and 2 (referred to collectively as Pdm), and Castor (Cas), identifies a transcription factor network regulating the temporal development of all ganglia. The Zn-finger proteins Hb and Cas, acting as repressors, confine Pdm expression to a narrow intermediate temporal window; this results in the generation of three panneural domains whose cellular constituents are marked by expression of Hb, Pdm, or Cas (R. Kambadur et al., 1998, Genes Dev. 12, 246-260). Seeking to identify the cellular mechanisms that generate these expression compartments, we studied the lineage development of isolated NBs in culture. We found that the Hb, Pdm, and Cas expression domains are generated by transitions in NB gene expression that are followed by gene product perdurance within sequentially produced sublineages. Our results also indicate that following Cas expression, many CNS NBs continue their asymmetric divisions generating additional progeny, which can be identified by the expression of the bHLH transcription factor Grainyhead (Gh). Gh appears to be a terminal embryonic CNS lineage marker. Taken together, these studies indicate that once NBs initiate lineage development, no additional signaling between NBs and the neuroectoderm and/or mesoderm is required to trigger the temporal progression of Hb --> Pdm --> Cas --> Gh expression during NB outgrowth.

Insights into neural stem cell biology from flies

“…(c) Entry into quiescence As mentioned previously, isolated embryonic neuroblasts appear to faithfully recapitulate their division patterns in vitro (Huff et al 1989;Brody & Odenwald 2000). If this is indeed the case, it may be that their final temporal state is quiescence, and that this state is regulated by an intrinsic (intra-clonal) neuroblast 'clock'.…”

“…GMCs and their neuronal progeny maintain expression of the transcription factor that is present in the neuroblast at the time of the GMC's birth. Thus, Hb is detected in deep layer neurons, with Kr, Pdm and Cas found in progressively more superficial layers (figure 5a; Kambadur et al 1998;Brody & Odenwald 2000;Isshiki et al 2001). The expression of these transcription factors correlates with birth order and not with a particular cell type.…”

“…The majority of embryonic neuroblasts sequentially express the transcription factors Hunchback (Hb), Kruppel (Kr), Pdm and Castor (Cas;Brody & Odenwald 2000;Isshiki et al 2001). GMCs and their neuronal progeny maintain expression of the transcription factor that is present in the neuroblast at the time of the GMC's birth.…”

Connecting Temporal Identity to Mitosis: The Regulation of Hunchback in Drosophila Neuroblast Lineages

“…1 Therefore, not much is known about the molecular mechanisms regulating these processes in vertebrates. In contrast in Drosophila, temporal identity genes have been identified [11][12][13][14][15] which are active during embryonic neuroblast lineage development. Insect neuroblasts (NBs) are neural stem cells budding off a chain of ganglion mother cells (GMCs) which subsequently divide once to generate a pair of postmitotic cells differentiating into neurons and/or glia.…”

“…In Drosophila, this change of identity is linked to a sequential expression of the transcription factors Hunchback (Hb), Krüppel (Kr), the coexpressed Pdm1 and 2 (also known as Nubbin and Miti-mere, respectively), 20,21 Castor (Cas, also known as Ming) 22,23 and Grainyhead (Grh). 11 These genes are consecutively expressed in a given NB in a certain time window. At the end of each phase, the expression is switched off in the NB but is maintained in the newly born GMC and its progeny.…”