Revisiting the Drosophila microchaete lineage

During animal development, cell fate diversity is generated in part by intrinsically asymmetric cell division, in which a mother cell divides to generate daughters of different developmental potential (Horvitz and Herskowitz, 1992). This process requires the coordination of two events: the mother cell must have an uneven distribution of cell-fate determinants and the mitotic spindle must be oriented so that, upon division, daughter cells receive different amounts of these determinants (Rhyu and Knoblich, 1995). In many cases, the orientation of asymmetric cell divisions is also determined relative to the body and/or tissue axes. The cell lineage generating the mechanosensory bristle of the adult fly provides a genetic model system to study the process of oriented asymmetric cell division at the molecular level (Posakony, 1994). In the notum, each bristle mechanosensory organ is composed of four different cells that originate from a single precursor cell (pI) after two rounds of asymmetric divisions (Hartenstein and Posakony, 1989; Fig. 1). Microchaete pI cells are specified in a regular pattern of rows in the dorsocentral region of the notum, around 6-9 hours after puparium formation (APF) (Usui and Kimura, 1993) and divide asymmetrically around 16 hours APF to generate two secondary precursors, pIIa and pIIb. The pIIa/pIIb fate decision is regulated by the differential activation of the Notch signaling pathway, which is activated in pIIa and inhibited in pIIb (Hartenstein and Posakony, 1990; Posakony, 1994). A negative regulator of Notch signalling, the membrane-associated Numb protein, is localized in a cortical crescent in mitotic pI and asymmetrically segregates into one of its daughter cells (Rhyu et al., 1994; Guo et al., 1996). Notch signalling is specifically inhibited in the cell that inherits Numb. This cell therefore adopts a pIIb fate. According to the lineage proposed by Hartenstein and Posakony (1989), pIIa divides first to generate the socket and shaft cells, while pIIb divides later to produce the sheath cell and neurone (Fig. 1). The identities of the pIIa and pIIb daughter cells are again regulated by the unequal segregation of Numb at mitosis and the inhibition of Notch signalling in the cells that inherit Numb. Notch signalling is activated in the socket and sheath cells, and inhibited in the shaft cell and neurone, which specifically inherit Numb (Zeng et al., 1998; Wang et al., 1997; Posakony, 1994; Gho and Schweisguth, 1998). Recently, Prospero, a divergent homeodomain transcription factor expressed in pIIb, but not in pIIa, has also 3573 Development 126, 3573-3584 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 DEV7736