Differential control of cell death and gene expression during two distinct phases of hormonally-regulated muscle death in the tobacco hawkmoth Manduca sexta.

In larvae of the tobacco hawkmoth Manduca sexta, the intersegmental muscles (ISMs) span eight abdominal segments and represent the major muscle group. Following pupation, the ISMs in the first two and last two segments undergo programmed cell death (PCD), while the remaining four segments persist until the time of adult eclosion, when they too undergo PCD. ISM death at adult eclosion is initiated by a decline in the circulating ecdysteroid titer and requires de novo gene expression.

Loss of notch activity in the developing central nervous system leads to increased cell death.

Many cells in the mammalian brain undergo apoptosis as a normal and critical part of development but the signals that regulate the survival and death of neural progenitor cells and the neurons they produce are not well understood. The Notch signaling pathway is involved in multiple decision points during development and has been proposed to regulate the survival and apoptosis of neural progenitor cells in the developing brain; however, previous experiments have not resolved whether Notch activity is pro- or anti-apoptotic. To elucidate the function of Notch signaling in the survival and death of cells in the nervous system, we have produced single and compound Notch conditional mutants in which Notch1 and Notch3 are removed at different times during brain development and in different populations of cells.

Notch 1 inhibits photoreceptor production in the developing mammalian retina.

The transmembrane receptor Notch1 plays a role in development and homeostasis in vertebrates and invertebrates. The mammalian retina is an excellent tissue in which to dissect the precise role of Notch signaling in regulating cell fate and proliferation. However, a systematic analysis has been limited by the early embryonic lethality of Notch1-null mice.

Notch signaling coordinates the patterning of striatal compartments.

Numerous lines of evidence suggest that Notch signaling plays a pivotal role in controlling the production of neurons from progenitor cells. However, most experiments have relied on gain-of-function approaches because perturbation of Notch signaling results in death prior to the onset of neurogenesis. Here, we examine the requirement for Notch signaling in the development of the striatum through the analysis of different single and compound Notch1 conditional and Notch3 null mutants.

Brain lipid-binding protein is a direct target of Notch signaling in radial glial cells.

Radial glia function during CNS development both as neural progenitors and as a scaffolding supporting neuronal migration. To elucidate pathways involved in these functions, we mapped in vivo the promoter for Blbp, a radial glial gene. We show here that a binding site for the Notch effector CBF1 is essential for all Blbp transcription in radial glia, and that BLBP expression is significantly reduced in the forebrains of mice lacking the Notch1 and Notch3 receptors.