Sall3 is required for the terminal maturation of olfactory glomerular interneurons

Abstract

Sall3 is a zinc finger containing putative transcription factor and a member of the Sall gene family. Members of the Sall gene family are highly expressed during development. Sall3-deficient mice die in the perinatal period because of dehydration and display alterations in palate formation and cranial nerve formation (Parrish et al. [2004] Mol Cell Biol 24:7102-7112). We examined the role of Sall3 in the development of the olfactory system. We determined that Sall3 is expressed by cells in the olfactory epithelium and olfactory bulb. Sall3 deficiency specifically alters formation of the glomerular layer. The glomerular layer was hypocellular, because of a decrease in the number of interneurons. The lateral ganglionic eminence and rostral migratory stream developed normally in Sall3-deficient animals, which suggests that Sall3 is not required for the initial specification of olfactory bulb interneurons. Fewer GAD65/67-, Pax6-, calretinin-, and calbindin-positive cells were detected in the glomerular layer, accompanied by an increase in cells positive for these markers in the granule cell layer. In addition, a complete absence of tyrosine hydroxylase expression was observed in the olfactory bulb in the absence of Sall3. However, expression of Nurr1, a marker of dopaminergic precursors, was maintained, indicating that dopaminergic precursors were present. Our data suggest that Sall3 is required for the terminal maturation of neurons destined for the glomerular layer. Indexing termsSpalt; 18q deletion syndrome; tyrosine hydroxylase; olfactory bulbThe olfactory bulb (OB) is a laminar structure containing two distinct neuronal populations. Excitatory projection neurons populate the mitral cell layer (MCL), and interneuron populations are located in the glomerular layer (GL) and granule cell layer (GCL), superficial and deep to the MCL respectively. OB neuronal populations are sequentially produced and have distinct origins. Mitral cells are the firstborn OB population (Hinds, 1968). These cells arise in the pallium, and the transcription factor Tbr1 is required for their generation (Bulfone et al., 1998;Moreno et al., 2003;Puelles et al., 2000). OB interneurons arise from an ER81-positive population in the subpallial dorsal lateral ganglionic eminence (LGE) and migrate to the OB via the rostral migratory stream (RMS; Doetsch and Alvarez-Buylla, 1996;Lois and Alvarez-Buylla, 1994;Stenman et al., 2003;Wichterle et al., 1999Wichterle et al., , 2001 Previous studies determined that OB interneurons are continuously generated throughout life (Altman, 1969;Altman and Das, 1966;Doetsch and Alvarez-Buylla, 1996;Hinds, 1968;Lois and Alvarez-Buylla, 1994;Luskin, 1993); however, mechanisms that regulate the generation of this diverse cellular population are not well characterized. OB interneurons begin to express mature interneuron markers as they terminally differentiate and radially migrate in the OB. The OB comprises chemically distinct interneuron populations; at least three subtypes have been identified characterized...

Brainstem galanin‐synthesizing neurons are differentially activated by chemoreceptor stimuli and represent a subpopulation of respiratory neurons

“…Indirect immunoblot analysis of proteins obtained from rat PC-12 pheochromocytoma cells recognizes a single band of $60kDa corresponding to rat TH (manufacturer's specifications). Staining in the rat brain with this TH antibody corresponds to previous studies reporting TH staining in different parts of rat brain (Harrison et al, 2008). Immunofluorescent staining of sections throughout the medulla oblongata of rats produced a pattern of TH immunoreactivity identical to previous descriptions (Armstrong et al, 1982).…”

Sall3 Correlates with the Expression of TH in Mouse Olfactory Bulb

“…In Sall3-null mice, a complete absence of TH expression is observed in the OB. But in the ventral midbrain, the expression of TH remains (Harrison et al 2008). Interestingly, in Nurr1-deficient mice, TH expression is absent from the substantial nigra and nigrostriatal pathway but is maintained in the OB (Le et al 1999).…”

“…Previous studies showed that the Sall3-deficient animals exhibited a complete absence of TH + cells in the OBs throughout development (Harrison et al 2008). This phenotype may be caused by a regulation function of Sall3 on TH gene expression.…”

“…OB DA neurons comprise a 10-16% population of OB periglomerular interneurons (De Marchis et al 2007;Parrish-Aungst et al 2007;Harrison et al 2008). Previous studies showed that the Sall3-deficient animals exhibited a complete absence of TH + cells in the OBs throughout development (Harrison et al 2008).…”

NeuroD1 induces terminal neuronal differentiation in olfactory neurogenesis

“…Several transcription factors have been implicated in the specification of the different neuronal populations. The zinc finger transcription factor sp8, for instance, appears to be involved in the generation of interneurons expressing calretinin (8), and analysis of Sall3 mutant mice (9) points to a role of this factor in the dopaminergic, tyrosine hydroxylase-positive lineage (10). Furthermore, it appears that interneuron diversity relies on the combinatorial expression of such transcription factors.…”