Ancestry-independent fate specification and plasticity in the developmental timing of a typical Drosophila neuronal lineage.
ABSTRACT In the Drosophila CNS, combinatorial, interdependent, sequential genetic programs in neuroectodermal (NE) cells, prior to the formation of neuroblasts (NBs), determine the initial identity of NBs. Temporal factors are then sequentially expressed to change the temporal identity. It is unclear at what levels this positional and temporal information integrates to determine progeny cell identity. One idea is that this is a top-down linear process: the identity of a NB determines the identity of its daughter, the ganglion mother cell (GMC), the asymmetric division of the GMC and the fate specification of daughter cells of the GMC. Our results with midline (mid), which encodes a T-box protein, in a typical lineage, NB4-2-->GMC-1-->RP2/sib, suggest that at least part of the process operates in GMCs. That is, a GMC or a neuronal identity need not be determined at the NB or NE level. This is demonstrated by showing that Mid is expressed in a row 5 GMC (M-GMC), but not in its parent NB or NE cell. In mid mutants, M-GMC changes into GMC-1 and generates an RP2 and a sib without affecting the expression of key genes at the NE/NB levels. Expression of Mid in the M-GMC in mid mutants rescues the fate change, indicating that Mid specifies neurons at the GMC level. Moreover, we found a significant plasticity in the temporal window in which a neuronal lineage can develop. Although the extra GMC-1 in mid mutants is born approximately 2 hours later than the bona fide GMC-1, it follows the same developmental pattern as the bona fide GMC-1. Thus, a GMC identity can be independent of parental identity and GMC formation and elaboration need not be strictly time-bound.
Article: On the functional overlap between two Drosophila POU homeo domain genes and the cell fate specification of a CNS neural precursor.[show abstract] [hide abstract]
ABSTRACT: The approximately 200 distinct neurons comprising each hemisegment of the Drosophila embryonic CNS are derived from a stereotypic array of approximately 30 progenitor stem cells, called neuroblasts (NBs). Each NB undergoes repeated asymmetric divisions to produce several smaller ganglion mother cells (GMCs), each of which, in turn, divides to produce two neurons and/or glia cells. To understand the process by which cell type diversity is generated in the CNS, we are focusing on identifying genes that affect cell identity in the NB4-2 lineage from which the RP2 motoneuron is derived. We show here that within the early part of the NB4-2 lineage, two closely linked and structurally related POU homeo domain genes, pdm-2 (dPOU28) and pdm-1 (dPOU19), both encode proteins that accumulate to high levels only in the first GMC (GMC4-2a) and not in its progeny, the RP2 motoneuron. Our results from the genetic and developmental analysis of pdm-1 and pdm-2 demonstrate that these genes are not required for the birth of GMC4-2a; however, they are both involved in specifying the identity of GMC4-2a and, ultimately, in the genesis of RP2 neurons, with pdm-2 being the more dominant player in this process. In mutant animals where both pdm-1 and pdm-2 functions are removed, GMC4-2a fails to express markers consistent with a GMC4-2a identity and no mature (Eve protein expressing) RP2 neurons are produced. We demonstrate that in some mutant combinations in which no mature RP2 neurons are produced, some GMC4-2a cells can nevertheless divide. Hence, the failure of the POU mutants to produce mature RP2 neurons is not attributable to a block in GMC4-2a cell division per se but, rather, because the GMC4-2a cells fail to acquire their correct cellular identity.Genes & Development 06/1995; 9(10):1223-36. · 11.66 Impact Factor