Math1 Expression Redefines the Rhombic Lip Derivatives and Reveals Novel Lineages within the Brainstem and Cerebellum

Abstract

The rhombic lip (RL) is an embryonic proliferative neuroepithelium that generates several groups of hindbrain neurons. However, the precise boundaries and derivatives of the RL have never been genetically identified. We use beta-galactosidase expressed from the Math1 locus in Math1-heterozygous and Math1-null mice to track RL-derived cells and to evaluate their developmental requirements for Math1. We uncover a Math1-dependent rostral rhombic-lip migratory stream (RLS) that generates some neurons of the parabrachial, lateral lemniscal, and deep cerebellar nuclei, in addition to cerebellar granule neurons. A more caudal Math1-dependent cochlear extramural stream (CES) generates the ventral cochlear nucleus and cochlear granule neurons. Similarly, mossy-fiber precerebellar nuclei require Math1, whereas the inferior olive and locus coeruleus do not. We propose that Math1 expression delimits the extent of the rhombic lip and is required for the generation of the hindbrain superficial migratory streams, all of which contribute neurons to the proprioceptive/vestibular/auditory sensory network.

Genetic inducible fate mapping in mouse: Establishing genetic lineages and defining genetic neuroanatomy in the nervous system

“…LacZ protein as a short-term cumulative marker as well with Math1-Cre cumulative fate mapping (Table 1; Landsberg et al, 2005;Wang et al, 2005; and see Wingate, 2005). Importantly, these studies illustrate that the various nuclei derived from the URL of r1 are precisely delineated early, based on the timing of expression of one gene.…”

“…GIFM, Genetic Inducible Fate Maping; Hb, hindbrain; E, embryonic day; URL, upper rhombic lip; nd, not determined; LRL, lower rhombic lip; n., nuclei; ߛ, contribution; -, no contribution. b X-Cre marking indicates cumulative marking approaches with references as follows: 1, Wnt1-Flp (Rodriguiz and Dymecki, 2000;Awatramani et al, 2003;Landsberg et al, 2005); 2, Gdf7-Cre (Currle et al, 2005); 3, En1-Cre (Zervas et al, 2004;Machold and Fishell, 2005); and 4, Math1-LacZ (Wang et al, 2005; lacZ perdurance as a cumulative approach) and Math1-Cre (Landsberg et al, 2005). c Only a small number of positive granule cells was observed in posterior Cb.…”

“…By taking advantage of the Wnt1 gradient and the fact that one Flp transgene (FlpL) marks a smaller region than a second Flp transgene (Flpe), the LRL can be fate mapped into two broad domains (Landsberg et al, 2005). Furthermore, the Wnt1-Flp marked domain appears to correspond to most of the Math1-CreER/-lacZ/-Cre domain (Machold and Fishell, 2005;Wang et al, 2005;Landsberg et al, 2005). The LRL can be further partitioned into a most dorsal progenitor domain that expresses Gdf7 (Fig.…”

“…2A,AЈ; Currle et al, 2005;Landsberg et al, 2005). Of interest, the broad dorsal domain marked by Math1-CreER/-Cre/-lacZ and Wnt1-Flp/-CreER gives rise to precerebellar nuclei in the ventral Hb that project mossy fibers to the granule cells, whereas the broader Wnt1-Flpe domain also marks the inferior olive, which houses the climbing fiber neurons that project to the Purkinje cells Zervas et al, 2004;Landsberg et al, 2005;Machold and Fishell, 2005;Wang et al, 2005). GIFM with Wnt1-CreER showed that the temporal contribution of the Wnt1 lineage to precerebellar nuclei occurs beginning at E10.5 ( Fig.…”

Visualization of two distinct classes of neurons by gad2 and zic1 promoter/enhancer elements in the dorsal hindbrain of developing zebrafish reveals neuronal connectivity related to the auditory and lateral line systems

“…However, the embryological origins and molecular profiles of these interneurons remain largely unknown. Recent studies in mice demonstrated the involvement of Wnt1 and Math1 (Atoh1) in the development of the auditory-related cochlear nuclei from a part of the lower rhombic lip, the dorsal-most portion of the hindbrain proliferative neuroepithelium (Wang et al, 2005;Farago et al, 2006). Although these studies revealed the origins and molecular profiles of the auditory nuclei, the fates of specific neuronal types remained obscure due to the difficulty in distinguishing them during development.…”