A protein related to p21-activated kinase (PAK) that is involved in neurogenesis in the Drosophila adult central nervous system

Abstract

Brains are organized by the developmental processes generating them. The embryonic neurogenic phase of Drosophila melanogaster has been studied in detail at the genetic, cellular and molecular level. In contrast, much of what is known of postembryonic brain development has been gathered by neuroanatomical and gene expression studies. The molecular mechanisms underlying cellular diversity and structural organisation in the adult brain, such as the establishment of the correct neuroblast number, the spatial and temporal control of neuroblast proliferation, cell fate determination, and the generation of the precise pattern of neuronal connectivity, are largely unknown. In a screen for viable mutations affecting adult central brain structures, we isolated the mushroom bodies tiny (mbt) gene of Drosophila, which encodes a protein related to p21-activated kinase (PAK). We show that mutations in mbt primarily interfere with the generation or survival of the intrinsic cells (Kenyon cells) of the mushroom body, a paired neuropil structure in the adult brain involved in learning and memory.

p21-activated Protein Kinase 4 (PAK4) Interacts with the Keratinocyte Growth Factor Receptor and Participates in Keratinocyte Growth Factor-mediated Inhibition of Oxidant-induced Cell Death

“…We show that this interaction has functional relevance, because expression of a dominant negative mutant of PAK4 prevented the inhibition of oxidant-induced caspase-3 activation by KGF in epithelial cells. It is interesting to note that just as mice deficient in the KGF receptor show organ malformation with evidence of enhanced apoptosis of developing organs such as the lung (9, 10), Drosophila lacking the protein Mushroom Body Tiny (MBT), the closest known homolog of PAK4, also shows defects in organ development with a reduced number of Kenyon cells in a structure in the brain called the mushroom body (35).…”

P21 activated kinases

“…66 Mushroom Body Tiny (MBT) is a Drosophila Pak that falls into group B. 67 Mutations in the mbt gene result in a decreased number of Kenyon cells in the Drosophila mushroom body, a structure of Drosophila brain, indicating that it is important for the regulation of neuronal survival or proliferation. 67 In humans, Pak3 is so far the most clinically relevant Pak with respect to the nervous system.…”

“…67 Mutations in the mbt gene result in a decreased number of Kenyon cells in the Drosophila mushroom body, a structure of Drosophila brain, indicating that it is important for the regulation of neuronal survival or proliferation. 67 In humans, Pak3 is so far the most clinically relevant Pak with respect to the nervous system. This is because mutations in PAK3 have been linked to nonsyndromatic X-linked mental retardation (MRX).…”

Natural variation in Drosophila larval reward learning and memory due to a cGMP-dependent protein kinase

“…We tested this by quantifying olfactory conditioning when increasing expression of for-T2 in the mushroom bodies in for s larvae using the mushroom-body GAL4 drivers 201Y, H24, c739, and 30Y (Yang et al 1995;Melzig et al 1998). Figure 3A depicts the expression pattern in the mushroom bodies of each of these drivers in mid-third instar larvae.…”

“…Mushroom body drivers 201Y, 30Y, c739 (Yang et al 1995) (donated by Joel Levine, University of Toronto at Mississauga, Canada) were backcrossed nine generations into a w 1 ;for s background. H24 (Melzig et al 1998) (also donated by Joel Levine) was crossed into a w 1 ;for s background via third chromosome substitution. UAS-GFP (Bloomington Stock Center) was crossed onto a w 1 ;for s background via third chromosome substitution.…”