Associate Professor
Genetic and molecular mechanisms required for neural stem and progenitor
cells to generate the forebrain in development, and regenerate it
in adulthood.
Which Factors Regulate Neural Stem Cell Fates in the forebrain?
Early
in development, the brain starts off as a simple sheet of
neuroepithelial cells. My lab is interested in understanding
how this simple sheet of progenitor cells develops into the
adult forebrain and, in particular, into the adult cerebral
cortex, the part of our forebrains that we use for our highest
cognitive and perceptual functions. Essential to this understanding
is the identification of the signals that pattern the early
forebrain and that regulate the proliferation, cell fate choices,
and differentiation of neural stem cells and progenitor cells.
The primary approach we are using to test the roles of candidate
signaling molecules directly in vivo is a conditional
genetic approach in the mouse. This approach, which uses CRE/loxP
technology, allows us to test the function of particular factors
by deleting or overexpressing the genes that encode them specifically
in the forebrain. An important complementary approach is to
test any novel function observed in vivo for a particular
factor by challenging isolated progenitor cells in culture
with it and determining whether it is sufficient on its own
to affect cell fate (and if not, what other factors are needed
in combination). Some of our immediate goals are: 1) to further
characterize the roles of signaling molecules of the FGF,
BMP, and other families in prenatal forebrain development;
2) to begin examining the roles of these factors at later
stages (from birth to adulthood); and 3) inspired from what
we learn about the roles of signaling molecules in development,
to evaluate the feasibility of using genetically modified
neural precursor cells, alone or in combination with modified
cellular environments, to achieve regeneration of damaged
or diseased forebrains.
Selected Publications
Paek H, Gutin G, Hébert JM. (2009). FGF signaling is strictly required to maintain early telencephalic precursor cell survival. Development 136: 2457-2465.
Kang W, Wang LC, Shi S, Hébert JM. (2009) The transition from stem to progenitor cell is inhibited by FGF signaling during corticogenesis. in revision.
Fernandes M, Hébert JM. (2008). The ups and downs of holoprosencephaly, dorsal versus ventral patterning forces. J. Clin. Gen., 73: 413-423.
Hébert JM, Fishell G. (2008). The genetics of telencephalon patterning, some assembly required. Nat. Rev. Neurosci., 9: 678-685.
Fernandes M, Gutin G, Alcorn H, McConnell SK, Hébert JM. (2007). Mutations in the BMP pathway in mice supports the existence of two molecular classes of holoprosencephaly. Development 134: 3789-3794.
Hanashima C, Fernandes M, Hébert JM, Fishell G. (2007). The role of Foxg1 and dorsal midline signaling in the generation of Cajal-Retzius subtypes. J. Neurosci. 27: 11103-11111.
Tole S, Gutin G, Remedios R, Bhatnagar L, Hébert JM. (2006). Development of midline cell types and commissural axon tracts requires Fgfr1 in the cerebrum. Dev. Biol. 289: 141-151.
Gutin G, Fernandes M, Ornitz D, McConnell SK, Hébert JM. (2006). FGF acts independently of SHH to generate ventral telencephalic cells. Development 133:2937-2946.
Early
in development, the brain starts off as a simple sheet of
neuroepithelial cells. My lab is interested in understanding
how this simple sheet of progenitor cells develops into the
adult forebrain and, in particular, into the adult cerebral
cortex, the part of our forebrains that we use for our highest
cognitive and perceptual functions. Essential to this understanding
is the identification of the signals that pattern the early
forebrain and that regulate the proliferation, cell fate choices,
and differentiation of neural stem cells and progenitor cells.
The primary approach we are using to test the roles of candidate
signaling molecules directly in vivo is a conditional
genetic approach in the mouse. This approach, which uses CRE/loxP
technology, allows us to test the function of particular factors
by deleting or overexpressing the genes that encode them specifically
in the forebrain. An important complementary approach is to
test any novel function observed in vivo for a particular
factor by challenging isolated progenitor cells in culture
with it and determining whether it is sufficient on its own
to affect cell fate (and if not, what other factors are needed
in combination). Some of our immediate goals are: 1) to further
characterize the roles of signaling molecules of the FGF,
BMP, and other families in prenatal forebrain development;
2) to begin examining the roles of these factors at later
stages (from birth to adulthood); and 3) inspired from what
we learn about the roles of signaling molecules in development,
to evaluate the feasibility of using genetically modified
neural precursor cells, alone or in combination with modified
cellular environments, to achieve regeneration of damaged
or diseased forebrains.