Postnatal ontogeny of the transcription factor Lmx1b in the mouse central nervous system

Abstract

The expression profile of Lim homeodomain transcription factor Lmx1b in the mouse brain was investigated at different postnatal stages by immunohistochemistry and in situ hybridization. At postnatal day (P) 7, many Lmx1b-expressing neurons were found in the posterior hypothalamic area, supramammillary nucleus, ventral premammillary nucleus, and subthalamic nucleus. In the midbrain, numerous Lmx1b-expressing neurons were present in the substantia nigra pars compacta and ventral tegmental area. In the hindbrain, Lmx1b-expressing neurons were primarily observed in the raphe nuclei, parabrachial nuclei, principal sensory trigeminal nucleus, nucleus of the solitary tract, and laminae I-II of the medullary dorsal horn as well as spinal dorsal horn. Although expression levels diminished as postnatal life progressed, persistent expression throughout the first year of life was observed in many of these regions. In contrast, Lmx1b was present in a few brain regions (e.g., principal sensory trigeminal nucleus) only in early life with expression expiring by P60. Lmx1b was observed in dopaminergic neurons in the midbrain and serotonergic neurons in the hindbrain, as determined by double labeling with specific markers. In addition, we found that Lmx1b-expressing neurons are not GABAergic, and Lmx1b was colocalized with Tlx3 in the parabrachial nuclei, principal sensory trigeminal nucleus, nucleus of the solitary tract. as well as the medullary and spinal dorsal horns, suggesting that Lmx1b-expressing cells in these areas are excitatory neurons. Our data suggest that Lmx1b is involved in the postnatal maturation of certain types of neurons and maintenance of their normal functions in the adult brain.

Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons

“…1C and Fig. S1) were still detectable in aged (13-mo-old) mice, supporting previous reports (12)(13)(14).…”

Retracted:Lmx1b-Controlled Isthmic Organizer Is Essential for Development of Midbrain Dopaminergic Neurons

“…In addition, coexpression of TH and Lmx1b was observed at later embryonic stages, and it persisted from early postnatal stage to adulthood (data not shown). Thus, we confirmed previous results (Asbreuk et al, 2002;Andersson et al, 2006;Ono et al, 2007;Dai et al, 2008) that Lmx1b is expressed in mDA neurons throughout all developmental stages as well as in matured mDA neurons.…”

“…The following mouse antisense RNA probes were used: Fgf8 (Wassarman et al, 1997), Wnt1 (Danielian and McMahon, 1996), and Aldhla1 and Lmx1b (Ding et al, 2004). For immunostaining, the following primary antibodies were used: rabbit and mouse anti-TH (1:2000; Sigma), rabbit anti-Lmx1b (1:2000) (Dai et al, 2008), rabbit antiserotonin (1:5000; Sigma), rabbit anti-Nurr1 (1:500; Santa Cruz), rat anti-Dat (1:1000; Chemicon), rabbit anti-Vmat2 (Chemicon), goat antiFoxa2 (1:500; Santa Cruz), and rabbit anti-Pitx3 (gift from J. Peter H. Burbach, Rudolph Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands). Sections were incubated overnight at 4°C with the appropriate primary antibody diluted in 0.1% Triton X-100 and 10% normal donkey serum in PBS.…”

“…Lmx1b is widely expressed in developing CNS (Asbreuk et al, 2002;Dai et al, 2008), and it plays a key role in the development of serotonergic neurons in the raphe nuclei (Cheng et al, 2003;Ding et al, 2003) and spinal dorsal horn (Ding et al, 2004). On the other hand, isthmic organizer (IsO) is the local signaling center for patterning and growth of the mid/hindbrain region (Joyner et al, 2000;Simeone, 2000;Liu and Joyner, 2001;Wurst and Bally-Cuif, 2001;Nakamura et al, 2005), and Lmx1b expression at MHB is essential for the development of the tectum and cerebellum by controlling the initiation of Fgf8, the key protein for the IsO inductive activity, and the maintenance of expression of other IsO-related genes in mice (Guo et al, 2007).…”

Transformation of the cerebellum into more ventral brainstem fates causes cerebellar agenesis in the absence of Ptf1a function

“…S4A), arguing that the Lmx1b+ lineage in rh1 does not give rise to cerebellar neurons. Previously, it has been shown in mouse embryos that Lmx1b and Tlx3 are coexpressed in a subset of neurons of the parabrachial (PB) nuclei (33), which develop independently of the RL (34). The rhombomeric origin of the PB nuclei is poorly understood.…”