Overexpression of Hoxa2 in dorsal rhombomere 1

TY - JOUR

T1 - Overexpression of Hoxa2 in dorsal rhombomere 1

AU - Toole, L J

AU - Eddison, M

AU - Wingate, R J T

PY - 2001

Y1 - 2001

N2 - We have used both injection of RCAS(BP)Hoxa2 virus and electroporation of an RCAS(BP)Hoxa2 construct to drive ectopic Hoxa2 expression in the presumptive cerebellum in chick. Both virus injection and electroporation were carried out at E2 in ovo and eggs reincubated for a further 4 to 8 days. While the gross morphology of the cerebellum is largely normal, the expression of granule cell markers (Pax6, ErbB4, Zic1) is severely reduced when ectopic Hoxa2 is expressed at the rhombic lip. This is consistent with a homeotic transformation of rhombomere (r)1 fate to that of r2 (which does not produce granule cell precursors). This agrees with observed changes in motor neuron fate in ventral r1 (Jungbluth S, Bell E, Lumsden A (1999) Development 126:2751-2758). However, further investigation revealed that the presumed reassignment of r1 segmental identity is incomplete. Paradoxically, Hoxa2 overexpression in dorsal r1 also results in an upregulation of Phox2a expression, which in r2 characterises only ventrally situated motor neurons. Within dorsal r1, Phox2a identifies neurons of the locus coeruleus which are induced by isthmic signals and which ultimately migrate into a ventral position. These observations, which are apparently inconsistent with Hoxa2 effecting a homeotic transformation in dorsal r1, suggest that patterning influences from the r1/midbrain isthmus may operate independently of segmental cues. The loss of granule cell markers accompanied by an increase in Phox2a positive neurons suggest that a single dorsal precursor might give rise to both locus coeruleus and rhombic lip precursors.

AB - We have used both injection of RCAS(BP)Hoxa2 virus and electroporation of an RCAS(BP)Hoxa2 construct to drive ectopic Hoxa2 expression in the presumptive cerebellum in chick. Both virus injection and electroporation were carried out at E2 in ovo and eggs reincubated for a further 4 to 8 days. While the gross morphology of the cerebellum is largely normal, the expression of granule cell markers (Pax6, ErbB4, Zic1) is severely reduced when ectopic Hoxa2 is expressed at the rhombic lip. This is consistent with a homeotic transformation of rhombomere (r)1 fate to that of r2 (which does not produce granule cell precursors). This agrees with observed changes in motor neuron fate in ventral r1 (Jungbluth S, Bell E, Lumsden A (1999) Development 126:2751-2758). However, further investigation revealed that the presumed reassignment of r1 segmental identity is incomplete. Paradoxically, Hoxa2 overexpression in dorsal r1 also results in an upregulation of Phox2a expression, which in r2 characterises only ventrally situated motor neurons. Within dorsal r1, Phox2a identifies neurons of the locus coeruleus which are induced by isthmic signals and which ultimately migrate into a ventral position. These observations, which are apparently inconsistent with Hoxa2 effecting a homeotic transformation in dorsal r1, suggest that patterning influences from the r1/midbrain isthmus may operate independently of segmental cues. The loss of granule cell markers accompanied by an increase in Phox2a positive neurons suggest that a single dorsal precursor might give rise to both locus coeruleus and rhombic lip precursors.

M3 - Meeting abstract

VL - 27

SP - 1228

JO - Society for Neuroscience Abstracts

JF - Society for Neuroscience Abstracts

IS - 1

T2 - 31st Annual Meeting of the Society for Neuroscience; Parts, Structures & Systems of Organisms: cerebellum: nervous system; dorsal rhombomere 1: nervous system; dorsal rhombomere 2: nervous system; egg: reproductive system; locus coeru

Y2 - 1 January 2001

ER -