CNS Expression Pattern of Lmx1b and Coexpression with Ptx Genes Suggest Functional Cooperativity in the Development of Forebrain Motor Control Systems

Asbreuk, C.H.J; Vogelaar, Christina Francisca; Hellemons, Anita J. C. G. M.; Smidt, Marten P.; Burbach, J. Peter H.

doi:10.1006/mcne.2002.1182

Cited by 55 publications

(66 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.…”

Section: Lmx1b Is Expressed In Mda Neuronssupporting

confidence: 93%

“…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).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Guo¹,

Qiu²,

Shi

et al. 2008

J. Neurosci.

View full text Add to dashboard Cite

The LIM homeodomain transcription factor Lmx1b has been suggested to be required for the differentiation of midbrain dopaminergic (mDA) neurons. However, whether the loss of mDA neurons in Lmx1b Ϫ/Ϫ mice is due to its intrinsic role in the mDA lineage or to a consequence of the malformations caused by the earlier mid/hindbrain patterning defects remains to be clarified. We report here that Lmx1b expression in mDA neurons is dispensable for their differentiation and maintenance, and the loss of mDA neurons in Lmx1b

show abstract

Section: Lmx1b Is Expressed In Mda Neuronssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

Guo¹,

Qiu²,

Shi

et al. 2008

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…We hypothesized that hypothalamic neuronal migration defects arise due to disrupted gene expression in hypothalamic neurons. To test this hypothesis, we analyzed expression of Lmx1b, a LIM homeodomain transcription factor expressed in the subthalamic nucleus and posterior hypothalamus which regulates development of serotonergic and dopaminergic neurons (Smidt et al, 2000;Asbreuk et al, 2002;Ding et al, 2003;Guo et al, 2007). We found, by double immunofluorescence, that PITX2 and LMX1B colocalize extensively in the E14.5 subthalamic nucleus and medial hypothalamus (data not shown).…”

Section: Pitx2 Mutant Neurons Retain Some Of Their Molecular Fatesmentioning

confidence: 99%

Cre fate mapping reveals lineage specific defects in neuronal migration with loss of Pitx2 function in the developing mouse hypothalamus and subthalamic nucleus

Skidmore

Cramer

Martin

et al. 2008

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

Establishment of neuronal diversity is a central topic in developmental neurobiology. Prior studies implicated Pitx2, a paired-like homeodomain transcription factor, in mouse subthalamic nucleus neuronal development, but precise stages of neuronal differentiation affected (migration, axon outgrowth, fate specification) and underlying mechanisms were unknown. Here we report lineage tracing experiments using Pitx2 cre/+ , Pitx2 cre/null , and conditional nuclear lacZ reporter mice to track embryonic Pitx2 expressing neurons. Migration of subthalamic nucleus and hypothalamic neurons was severely arrested in Pitx2 cre/null embryos, and subclasses of subthalamic nucleus neurons identified by Lmx1b, Foxp1, and Foxp2-gene expression revealed differing sensitivities to Pitx2 dosage. Interestingly, embryonic subthalamic nucleus development was unaffected in Lmx1b null mice, suggesting that Pitx2 and Lmx1b act via independent genetic pathways. These data provide the first direct evidence for Pitx2-dependent neuronal migration in the developing hypothalamus, and demonstrate that complex transcriptional networks regulate regional specialization of distinct hypothalamic and subthalamic nucleus neurons.

show abstract

“…Its mutation in human causes a dominantly inherited disease called nail-patella syndrome (Chen et al, 1998;Morello et al, 2001). During CNS development, Lmx1b is essential for the differentiation of midbrain dopaminergic neurons, hindbrain serotonergic neurons, and medullary and spinal dorsal horn neurons (Asbreuk et al, 2002;Cheng et al, 2003;Ding et al, 2003;Ding et al, 2004;Smidt et al, 2000). In addition to its well known function in neuronal differentiation, Lmx1b is expressed in Lmx1b is essential for Fgf8 and Wnt1 expression in the isthmic organizer during tectum and cerebellum development in mice the developing MHB in chick and zebrafish, and misexpression of Lmx1b in the MHB of the chick embryo causes expansion of the tectum and cerebellum and induces Fgf8 and Wnt1 expression (Adams et al, 2000;Matsunaga et al, 2002), whereas knockdown of lmx1b in the zebrafish results in the loss of isthmic and cerebellar structures and the loss of fgf8 and wnt1 expression as well (O'Hara et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Lmx1bis essential forFgf8andWnt1expression in the isthmic organizer during tectum and cerebellum development in mice

et al. 2007

View full text Add to dashboard Cite

Secreted factors FGF8 and WNT1 are essential either for the inductive activity of the isthmus organizer or for the regionalization of the midbrain-hindbrain boundary (MHB). However, transcriptional regulation of these secreted factors during development remains to be elucidated. Here we show that the LIM homeobox gene Lmx1b is expressed in the anterior embryo as early as E7.5 and its expression becomes progressively restricted to the isthmus at E9.0. Analysis of gene expression in the MHB of the mutant embryos showed that many genes were lost by E9.5. In the MHB of Lmx1b -/-embryos, the expression of Fgf8, which normally occurs at the 4-somite stage, was completely absent, whereas Wnt1 was downregulated before the 4-somite stage. Moreover, transcription factors En1 and Pax2 were also downregulated prior to the 4-somite stage, whereas Gbx2 downregulation occurred at the 4-somite stage. By contrast, Otx2 and Pax6 expression was not affected in Lmx1b -/-embryos. The requirement of specific Lmx1b expression in the MHB was further confirmed by Wnt1-Cre-mediated region-specific conditional knockout of Lmx1b. As a result of these molecular defects, the development of the tectum and cerebellum was severely impaired in Lmx1b -/-mice. Taken together, our results indicate that Lmx1b plays an essential role in the development of the tectum and cerebellum by regulating expression of Fgf8, Wnt1 and several isthmus-related transcription factors in the MHB, and is a crucial component of a cross-regulatory network required for the induction activity of the isthmic organizer in the MHB.

show abstract

CNS Expression Pattern of Lmx1b and Coexpression with Ptx Genes Suggest Functional Cooperativity in the Development of Forebrain Motor Control Systems

Cited by 55 publications

References 65 publications

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

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

Cre fate mapping reveals lineage specific defects in neuronal migration with loss of Pitx2 function in the developing mouse hypothalamus and subthalamic nucleus

Lmx1bis essential forFgf8andWnt1expression in the isthmic organizer during tectum and cerebellum development in mice

Contact Info

Product

Resources

About