Tole, S., Remedios, R., Saha, B. & Stoykova, A. Selective requirement of Pax6, but not Emx2, in the specification and development of several nuclei of the amygdaloid complex. J. Neurosci. 25, 2753-2760
The amygdaloid complex is a group of nuclei that are thought to originate from multiple sites of the dorsal and ventral telencephalic neuroepithelium. The mechanisms that regulate their development are essentially unknown. We studied the role of Pax6 and Emx2, two transcription factors that regulate regional specification and growth of the telencephalon, in the morphogenesis of the amygdaloid complex. We used a set of specific marker genes that identify distinct amygdaloid nuclei to analyze Pax6/Small eye and Emx2 knock-out mutant mouse brains. We found that there is a selective requirement for Pax6, but not Emx2, in the formation a subset of nuclei within the amygdaloid complex. Specifically, structures that were not previously considered to be developmentally linked, the nucleus of the lateral olfactory tract and the lateral, basolateral, and basomedial nuclei, all appear to have a common requirement for Pax6. Together, our findings provide new insights into the origins and mechanisms underlying the development of the amygdaloid complex.
"In neocortical development, Emx2, Pax6 and FGFs act in counterbalance . Pax6 deficiency results in an areal expansion of visual cortex, a reduction of frontal areas, and dysgenesis of limbic structures (Stoykova et al., 2000; Tole et al., 2005). On the other hand, Emx2 deficiency produces an expansion of frontal regions and a reduction of occipital regions (visual cortex; Bishop et al., 2000). "
[Show abstract][Hide abstract] ABSTRACT: The anatomical organization of the mammalian neocortex stands out among vertebrates for its laminar and columnar arrangement, featuring vertically oriented, excitatory pyramidal neurons. The evolutionary origin of this structure is discussed here in relation to the brain organization of other amniotes, i.e., the sauropsids (reptiles and birds). Specifically, we address the developmental modifications that had to take place to generate the neocortex, and to what extent these modifications were shared by other amniote lineages or can be considered unique to mammals. In this article, we propose a hypothesis that combines the control of proliferation in neural progenitor pools with the specification of regional morphogenetic gradients, yielding different anatomical results by virtue of the differential modulation of these processes in each lineage. Thus, there is a highly conserved genetic and developmental battery that becomes modulated in different directions according to specific selective pressures. In the case of early mammals, ecological conditions like nocturnal habits and reproductive strategies are considered to have played a key role in the selection of the particular brain patterning mechanisms that led to the origin of the neocortex.
Frontiers in Neuroanatomy 11/2013; 7:38. DOI:10.3389/fnana.2013.00038 · 3.54 Impact Factor
"In mouse embryos, the amygdalar derivatives of the ventral pallium are characterized by expression of Tbr1, Lhx2, and Lhx9 (Puelles et al., 2000; Medina et al., 2004; Tole et al., 2005; Garc ıa-L opez et al., 2008). These include part of the basal amygdalar complex, and the anterior and posteromedial cortical amygdalar areas. "
"The analysis of VP and CR cell specification in these mutants would shed new light into the mechanisms of areal patterning gene functions. For example, it is known that Pax6 plays a crucial role in VP specification (Assimacopoulos et al., 2003; Tole et al., 2005). "
[Show abstract][Hide abstract] ABSTRACT: The mammalian neocortex is a structure
with no equals in the vertebrates and is the seat of
the highest cerebral functions, such as thoughts and consciousness.
It is radially organized into six layers and
tangentially subdivided into functional areas deputed to
the elaboration of sensory information, association
between different stimuli, and selection and triggering
of voluntary movements. The process subdividing the
neocortical field into several functional areas is called
\arealization". Each area has its own cytoarchitecture,
connectivity, and peculiar functions. In the last century,
several neuroscientists have investigated areal structure
and the mechanisms that have led during evolution to
the rising of the neocortex and its organization. The
extreme conservation in the positioning and wiring of
neocortical areas among different mammalian families
suggests a conserved genetic program orchestrating neocortical
patterning. However, the impressive plasticity
of the neocortex, which is able to rewire and reorganize
areal structures and connectivity after impairments of
sensory pathways, argues for a more complex scenario.
Indeed, even if genetics and molecular biology helped in
identifying several genes involved in the arealization
process, the logic underlying the neocortical bauplan is
still beyond our comprehension. In this review, we will
introduce the present knowledge and hypotheses on the
ontogenesis and evolution of neocortical areas. Then, we
will focus our attention on some open issues, which are
still unresolved, and discuss some recent studies that
might open new directions to be explored in the next few
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