Molecular Fingerprint and Developmental Regulation of the Tegmental GABAergic and Glutamatergic Neurons Derived from the Anterior Hindbrain

Abstract

Highlights d GABAergic and glutamatergic precursors contribute to tegmental nuclei d The TF Tal1 and Notch signaling control neuron differentiation in the embryonic brainstem d TFs downstream of Tal1 mark and regulate development of specific tegmental nuclei

Inactivation of the GATA Cofactor ZFPM1 Results in Abnormal Development of Dorsal Raphe Serotonergic Neuron Subtypes and Increased Anxiety-Like Behavior

“…3A; data not shown). Similar to the Zfpm2 CKO embryos (Morello et al, 2020), the early production of rV2-derived GABAergic precursors was unaffected in Zfpm1 CKO mutants at E12.5 (data not shown). In contrast to the Zfpm2 CKO and Zfpm1 CKO ;Zfpm2 CKO mice, the pSNpr, RMTg, and VTg GABAergic neurons were present in the correct location and expressed their specific markers in Zfpm1 CKO mutants at E18.5 (Fig.…”

“…Zfpm1 is not required for the development of the r1-derived posterior substantia nigra pars reticulata, rostromedial tegmental nucleus, and ventral tegmental nucleus of Gudden GABAergic neurons In addition to the serotonergic precursors, Zfpm1 was expressed by the GABAergic precursors in the rV2 domain. These precursors contribute to multiple GABAergic nuclei in the ventral midbrain and anterior hindbrain, including the posterior substantia nigra pars reticulata (pSNpr), rostromedial tegmental nucleus (RMTg) and the ventral tegmental nucleus of Gudden (VTg; Achim et al, 2012;Lahti et al, 2016;Morello et al, 2020). In addition to Zfpm1, the GABAergic precursors in the rV2 also express ZFPM2 (Fig.…”

“…During the differentiation of several cell types, in particular in the hematopoietic system, GATA TFs interact with their zincfinger cofactor proteins ZFPM1 and ZFPM2 to repress or activate gene expression (Tsang et al, 1997;Fox et al, 1999;Lu et al, 1999;Tevosian et al, 2000;Robert et al, 2002;Pal et al, 2004;Beuling et al, 2008;Miccio et al, 2010;Chlon et al, 2012). During neuronal development, ZFPM2 was recently shown to be important for the full differentiation of corticothalamic projection neurons in developing cortex and GABAergic neuron subtypes in r1 (Galazo et al, 2016;Morello et al, 2020). The related cofactor ZFPM1 is also expressed in the DR serotonergic neuron precursors (Lahti et al, 2016), but the function of ZFPM1 in their differentiation is not understood.…”

Neurons gating behavior—developmental, molecular and functional features of neurons in the Substantia Nigra pars reticulata

“…Importantly, a hindbrain-specific Cre-driver ( Gbx2 CreERT 2 ) labeled the posterior part of the SNpr (pSNpr), but not its anterior part (aSNpr). Studies of the development of GABAergic neuron subtypes in the rhombomere 1 (r1) of the anterior hindbrain have further refined the origin of the pSNpr neurons in the ventrolateral r1 neuroepithelium expressing the homeodomain transcription factor (TF) NKX6-1, and in particular the anterior part of this neuroepithelial region close to the midbrain-hindbrain border ( Morello et al, 2020a ; Figure 2A ). On the other hand, fate mapping with the Nkx6-2 CreERT 2 –driver suggested that the aSNpr neurons are derived from the Nkx6-2 expressing neuronal progenitors or precursors found in the ventrolateral midbrain-diencephalon region ( Qiu et al, 1998 ; Moreno-Bravo et al, 2010 ; Madrigal et al, 2016 ).…”

Gata2, Nkx2-2 and Skor2 form a transcription factor network regulating development of a midbrain GABAergic neuron subtype with characteristics of REM sleep regulatory neurons

“…1B). From those, Gata3 , Tal1 , Tal2 , Zfpm1 and Zfpm2 have earlier been associated with the function of Gata2 or other Gata factors in different developmental contexts (Chlon and Crispino, 2012; Lahti et al, 2016; Morello et al, 2020; Tikker et al, 2020). ISH analysis showed that these putative Gata2 cofactors were broadly expressed in the E12.5 midbrain GABAergic neuron precursors (Fig.…”