Neuroepithelial secondary organizers and cell fate specification in the developing brain

Echevarrı́a, Diego; Vieira, Claudia; Gimeno, Lourdes

doi:10.1016/j.brainresrev.2003.08.002

Cited by 156 publications

(142 citation statements)

References 134 publications

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“…Fgf19 expression was localized in differentiating neurons close to the morphogenetic centers identified as secondary organizers, the zona limitans intrathalamica (zli) in the diencephalon and the isthmic organizer (IsO) in the mid-hindbrain boundary (Echevarria et al, 2003;Martinez, 2001). This was also observed for mouse Fgf15, whose expression pattern was complementary to Fgf19, that is, while chick Fgf19 was expressed in zli and isthmic mantle layers, Fgf15 was expressed in mouse just outside of the zli and isthmic neuroepithelium (Figs.…”

Section: Fgf19 In Relation To Fgf8 and Shh Expressionmentioning

confidence: 99%

Expression of chick Fgf19 and mouse Fgf15 orthologs is regulated in the developing brain by Fgf8 and Shh

Gimeno

Martı́nez

2007

Developmental Dynamics

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Fibroblast growth factors (Fgfs) constitute a family of signaling molecules that play essential roles in development. We have studied the expression pattern of mouse Fgf15 in the developing brain. Fgf19 is another member of the FGF family that has been suggested as the chick and human ortholog of mouse and rat Fgf15. Here, we compare the expression pattern during neural development of chick Fgf19 with mouse Fgf15. Unlike Fgf15, Fgf19 presents an expression in the isthmic alar plate, diencephalic and mesencephalic parabasal plates, hindbrain basal plate, as well as in the zona limitans intrathalamica (zli). Moreover, we explored the regulation between Fgf19 and the signaling molecules of the isthmic and zli organizers: Fgf8 and Shh, respectively. Considering the possibility that Fgf19 plays a similar role in humans and chicks, this finding could explain the significant diencephalic phenotypic differences between humans and mice in models and diseases where the Shh pathway is affected. Developmental Dynamics 236:2285-2297, 2007.

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Section: Fgf19 In Relation To Fgf8 and Shh Expressionmentioning

confidence: 99%

Expression of chick Fgf19 and mouse Fgf15 orthologs is regulated in the developing brain by Fgf8 and Shh

Gimeno

Martı́nez

2007

Developmental Dynamics

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“…Recently, several studies have examined the role of Fgf8 in the activity of two secondary organizers (Echevarría et al, 2003): the anterior neural ridge and the isthmic organizer (Chi et al, 2003;Alexandre et al, 2006;Nakamura et al, 2008). These regions are known to generate positional information controlling the histogenesis of neighboring domains.…”

Section: Introductionmentioning

confidence: 99%

The Development of the Thalamic Motor Learning Area Is Regulated by Fgf8 Expression

Martínez-Ferre¹,

Martı́nez²

2009

J. Neurosci.

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Habenular nuclei play a key role in the control of motor and cognitive behavior, processing emotion, motivation, and reward values in the brain. Thus, analysis of the molecular and cellular mechanisms underlying the development and evolution of this region will contribute to a better understanding of brain function. The Fgf8 gene is expressed in the dorsal midline of the diencephalon, close to the area in which the habenular region will develop. Given that Fgf8 is an important morphogenetic signal, we decided to investigate the role of Fgf8 signaling in diencephalic development. To this end, we analyzed the effects of altered Fgf8 expression in the mouse embryo, using molecular and cellular markers. Decreasing Fgf8 activity in the diencephalon was found to be associated with dosage-dependent alterations in the epithalamus: the habenular region and pineal gland are reduced or lacking in Fgf8 hypomorphic mice. Actually, our findings indicate that Fgf8 may be the master gene for these diencephalic domains, acting as an inductive and morphogenetic regulator. Therefore, the emergence of the habenular region in vertebrates could be understood in terms of a phylogenetic territorial addition caused by de novo expression of Fgf8 in the diencephalic alar plate. This region specializes to permit the development of adaptive control of the motor function in the vertebrate brain.

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“…The mid-hindbrain (MHB) organizer, marked by the expression of Fgf8 and Wnt1 at the isthmic constriction, is crucial for patterning and growth of the mes-met region (for review, see Simeone, 2000;Liu and Joyner, 2001;Nakamura, 2001;Rhinn and Brand, 2001;Wurst and Bally-Cuif, 2001;Echevarria et al, 2003;Raible and Brand, 2004). Mesencephalic and metencephalic progenitors are subsequently programmed by D-V signals from the roof plate and floor plate, including Bmps and Shh (Tanabe and Jessell, 1996).…”

Section: Introductionmentioning

confidence: 99%

Otx2 Regulates Subtype Specification and Neurogenesis in the Midbrain

Vernay¹,

Koch²,

Vaccarino³

et al. 2005

J. Neurosci.

132

117

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The transcription factor Otx2 is required to determine mesencephalic versus metencephalic (cerebellum/pons) territory during embryogenesis. This function of Otx2 primarily involves positioning and maintaining the mid-hindbrain organizer at the border between midbrain and anterior hindbrain. Otx2 expression is maintained long after this organizer is established. We therefore generated conditional mutants of Otx2 using the Cre/loxP system to study later roles during rostral brain development. For inactivation of Otx2 in neuronal progenitor cells, we crossed Otx2 flox/flox animals with Nestin-Cre transgenic animals. In Nestin-Cre/؉; Otx2 flox/flox embryos, Otx2 activity was lost from the ventral midbrain starting at embryonic day 10.5 (E10.5). In these mutant embryos, the mid-hindbrain organizer was properly positioned at E12.5, although Otx2 is absent from the midbrain. Hence, the Nestin-Cre/؉; Otx2 flox/flox animals represent a novel mouse model for studying the role of Otx2 in the midbrain, independently of abnormal development of the mid-hindbrain organizer.Our data demonstrate that Otx2 controls the development of several neuronal populations in the midbrain by regulating progenitor identity and neurogenesis. Dorsal midbrain progenitors ectopically expressed Math1 and generate an ectopic cerebellar-like structure. Similarly, Nkx2.2 ectopic expression ventrally into tegmentum progenitors is responsible for the formation of serotonergic neurons and hypoplasia of the red nucleus in the midbrain. In addition, we discovered a novel role for Otx2 in regulating neurogenesis of dopaminergic neurons. Altogether, these results demonstrate that Otx2 is required from E10.5 onward to regulate neuronal subtype identity and neurogenesis in the midbrain.

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Neuroepithelial secondary organizers and cell fate specification in the developing brain

Cited by 156 publications

References 134 publications

Expression of chick Fgf19 and mouse Fgf15 orthologs is regulated in the developing brain by Fgf8 and Shh

Expression of chick Fgf19 and mouse Fgf15 orthologs is regulated in the developing brain by Fgf8 and Shh

The Development of the Thalamic Motor Learning Area Is Regulated by Fgf8 Expression

Otx2 Regulates Subtype Specification and Neurogenesis in the Midbrain

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