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Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development.

Agoston Z, Li N, Haslinger A, Wizenmann A, Schulte D - BMC Dev. Biol. (2012)

Bottom Line: Much less, however, is known about the regulatory relationship and functional interaction of molecules that are expressed in the tectal anlage after tectal fate specification has taken place and tectal development has commenced.Here, we provide experimental evidence for reciprocal regulation and subsequent cooperation of the paired-type transcription factors Pax3, Pax7 and the TALE-homeodomain protein Meis2 in the tectal anlage.Physical interaction with Meis2 may then confer tectal specificity to a wide range of otherwise broadly expressed transcriptional regulators, including Otx2, Pax3 and Pax7.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Neurology (Edinger Institute), J, W, Goethe University Medical School, Heinrich Hoffmannstr, 7, 50628 Frankfurt, Germany.

ABSTRACT

Background: During early stages of brain development, secreted molecules, components of intracellular signaling pathways and transcriptional regulators act in positive and negative feed-back or feed-forward loops at the mid-hindbrain boundary. These genetic interactions are of central importance for the specification and subsequent development of the adjacent mid- and hindbrain. Much less, however, is known about the regulatory relationship and functional interaction of molecules that are expressed in the tectal anlage after tectal fate specification has taken place and tectal development has commenced.

Results: Here, we provide experimental evidence for reciprocal regulation and subsequent cooperation of the paired-type transcription factors Pax3, Pax7 and the TALE-homeodomain protein Meis2 in the tectal anlage. Using in ovo electroporation of the mesencephalic vesicle of chick embryos we show that (i) Pax3 and Pax7 mutually regulate each other's expression in the mesencephalic vesicle, (ii) Meis2 acts downstream of Pax3/7 and requires balanced expression levels of both proteins, and (iii) Meis2 physically interacts with Pax3 and Pax7. These results extend our previous observation that Meis2 cooperates with Otx2 in tectal development to include Pax3 and Pax7 as Meis2 interacting proteins in the tectal anlage.

Conclusion: The results described here suggest a model in which interdependent regulatory loops involving Pax3 and Pax7 in the dorsal mesencephalic vesicle modulate Meis2 expression. Physical interaction with Meis2 may then confer tectal specificity to a wide range of otherwise broadly expressed transcriptional regulators, including Otx2, Pax3 and Pax7.

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Meis2, Pax3 and Pax7 are expressed in nested domains in the HH15-19 chick midbrain. (A-G) Expression of Meis2 (A, D), Pax3 (B, E) and Pax7 (C, F) as detected by in-situ hybridization on HH15 whole chick embryos (A-C) or neighboring vibratome cross sections through a HH19 mesencephalic vesicle (D-F). (G) Schematic summary of the expression patterns. di: diencephalic vesicle; le: lens; mes: mesencephalic vesicle; met: metencephalic vesicle; rt: retina. The arrows in (D-F) mark the ventral border of the respective expression domains. Panel (D) was taken from [17].
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Figure 1: Meis2, Pax3 and Pax7 are expressed in nested domains in the HH15-19 chick midbrain. (A-G) Expression of Meis2 (A, D), Pax3 (B, E) and Pax7 (C, F) as detected by in-situ hybridization on HH15 whole chick embryos (A-C) or neighboring vibratome cross sections through a HH19 mesencephalic vesicle (D-F). (G) Schematic summary of the expression patterns. di: diencephalic vesicle; le: lens; mes: mesencephalic vesicle; met: metencephalic vesicle; rt: retina. The arrows in (D-F) mark the ventral border of the respective expression domains. Panel (D) was taken from [17].

Mentions: Two transcription factors reported to contribute to MHB organizer maintenance are the paired-box transcription factors Pax3 and Pax7 [11,12]. Both proteins share extensive homologies in protein sequence and expression patterns and are therefore believed to have arisen from a gene duplication event [13]. The importance of Pax3 in dorsal neural tube and neural crest patterning and differentiation is evident in the human syndromes associated with Pax3 mutations (Waardenburg syndromes type I and type III) as well as in mouse Splotch mutants. By contrast, Pax7 mutant mice do not display major defects in central nervous system development, which suggests a significant degree of functional overlap of the two Pax proteins [14,15]. In fact, knock-in of Pax7 can rescue the central nervous system and neural crest defects associated with the Pax3/Splotch mutant phenotype [16]. In chick embryos, Pax3 and Pax7 are expressed from the ten somite stage onwards in nested domains within the dorsal neural tube. By the 25-26 somite stage, mesencephalic Pax3 expression extends more ventrally than that of Pax7, whereas only Pax7 expression reaches rostrally into the telencephalic vesicle [[11]; and Figure 1). Although expression of both genes is not specific for the mid-hindbrain territory, ectopic expression of either one induced expression of MHB organizer associated genes including Fgf8 and En2 and elicited development of ectopic tectal structures [11].


Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development.

Agoston Z, Li N, Haslinger A, Wizenmann A, Schulte D - BMC Dev. Biol. (2012)

Meis2, Pax3 and Pax7 are expressed in nested domains in the HH15-19 chick midbrain. (A-G) Expression of Meis2 (A, D), Pax3 (B, E) and Pax7 (C, F) as detected by in-situ hybridization on HH15 whole chick embryos (A-C) or neighboring vibratome cross sections through a HH19 mesencephalic vesicle (D-F). (G) Schematic summary of the expression patterns. di: diencephalic vesicle; le: lens; mes: mesencephalic vesicle; met: metencephalic vesicle; rt: retina. The arrows in (D-F) mark the ventral border of the respective expression domains. Panel (D) was taken from [17].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3313853&req=5

Figure 1: Meis2, Pax3 and Pax7 are expressed in nested domains in the HH15-19 chick midbrain. (A-G) Expression of Meis2 (A, D), Pax3 (B, E) and Pax7 (C, F) as detected by in-situ hybridization on HH15 whole chick embryos (A-C) or neighboring vibratome cross sections through a HH19 mesencephalic vesicle (D-F). (G) Schematic summary of the expression patterns. di: diencephalic vesicle; le: lens; mes: mesencephalic vesicle; met: metencephalic vesicle; rt: retina. The arrows in (D-F) mark the ventral border of the respective expression domains. Panel (D) was taken from [17].
Mentions: Two transcription factors reported to contribute to MHB organizer maintenance are the paired-box transcription factors Pax3 and Pax7 [11,12]. Both proteins share extensive homologies in protein sequence and expression patterns and are therefore believed to have arisen from a gene duplication event [13]. The importance of Pax3 in dorsal neural tube and neural crest patterning and differentiation is evident in the human syndromes associated with Pax3 mutations (Waardenburg syndromes type I and type III) as well as in mouse Splotch mutants. By contrast, Pax7 mutant mice do not display major defects in central nervous system development, which suggests a significant degree of functional overlap of the two Pax proteins [14,15]. In fact, knock-in of Pax7 can rescue the central nervous system and neural crest defects associated with the Pax3/Splotch mutant phenotype [16]. In chick embryos, Pax3 and Pax7 are expressed from the ten somite stage onwards in nested domains within the dorsal neural tube. By the 25-26 somite stage, mesencephalic Pax3 expression extends more ventrally than that of Pax7, whereas only Pax7 expression reaches rostrally into the telencephalic vesicle [[11]; and Figure 1). Although expression of both genes is not specific for the mid-hindbrain territory, ectopic expression of either one induced expression of MHB organizer associated genes including Fgf8 and En2 and elicited development of ectopic tectal structures [11].

Bottom Line: Much less, however, is known about the regulatory relationship and functional interaction of molecules that are expressed in the tectal anlage after tectal fate specification has taken place and tectal development has commenced.Here, we provide experimental evidence for reciprocal regulation and subsequent cooperation of the paired-type transcription factors Pax3, Pax7 and the TALE-homeodomain protein Meis2 in the tectal anlage.Physical interaction with Meis2 may then confer tectal specificity to a wide range of otherwise broadly expressed transcriptional regulators, including Otx2, Pax3 and Pax7.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Neurology (Edinger Institute), J, W, Goethe University Medical School, Heinrich Hoffmannstr, 7, 50628 Frankfurt, Germany.

ABSTRACT

Background: During early stages of brain development, secreted molecules, components of intracellular signaling pathways and transcriptional regulators act in positive and negative feed-back or feed-forward loops at the mid-hindbrain boundary. These genetic interactions are of central importance for the specification and subsequent development of the adjacent mid- and hindbrain. Much less, however, is known about the regulatory relationship and functional interaction of molecules that are expressed in the tectal anlage after tectal fate specification has taken place and tectal development has commenced.

Results: Here, we provide experimental evidence for reciprocal regulation and subsequent cooperation of the paired-type transcription factors Pax3, Pax7 and the TALE-homeodomain protein Meis2 in the tectal anlage. Using in ovo electroporation of the mesencephalic vesicle of chick embryos we show that (i) Pax3 and Pax7 mutually regulate each other's expression in the mesencephalic vesicle, (ii) Meis2 acts downstream of Pax3/7 and requires balanced expression levels of both proteins, and (iii) Meis2 physically interacts with Pax3 and Pax7. These results extend our previous observation that Meis2 cooperates with Otx2 in tectal development to include Pax3 and Pax7 as Meis2 interacting proteins in the tectal anlage.

Conclusion: The results described here suggest a model in which interdependent regulatory loops involving Pax3 and Pax7 in the dorsal mesencephalic vesicle modulate Meis2 expression. Physical interaction with Meis2 may then confer tectal specificity to a wide range of otherwise broadly expressed transcriptional regulators, including Otx2, Pax3 and Pax7.

Show MeSH
Related in: MedlinePlus