Molecular Biology C SSheng Zhao ( ), Biochemistry and Molecular
Department of Medical school in Southeast University CCouse QQ
Club: 112342994 ( C ) WWeb: http://teaching.ewindup.info/ EEmail:
[email protected] or [email protected] QQQ /MSN/Skype/gChat:
[email protected] MMobile:18551669724 or 13675130010 Conception,
theory, research, and application Logic and LIY (Learn It Yourself)
Slide 2 Section 1 : How a song can change a genome From bird song
to infant language learning (Language learning and language
disorder) Section 2: Life rhythm Biological clock in photoperiod
animals (endocrine cycle and time for medicine) Case 3 : Taking
from the movie: Talk to her Human vegetables (Animal modeling for
Brain injury) Chapter 3: Rap A Gene Song (Disease research and
model animals) Slide 3 How a song can change a genome Slide 4
Language Human Language: A human capacity For acquiring and using
complex systems of communication Language development (acquiring):
soak up vocabulary, construct new sentences, invent etc.
Communication (Using) Estimates of the number of languages in the
world vary between 6,000 and 7,000. Human language is unique
because it has the properties of productivity, recursivity, and
displacement, and because it relies entirely on social convention
and learning. Slide 5 Language and Songbirds Many religions and
mythologies have considered the language of the birds to be a
symbol of great wisdom: The Norse god Odin had two songbirds, named
thought and mind, whose daily tweets were the source of his
knowledge on our mortal affairs. Slide 6 Why Songbirds Uniquely
human? If youre looking for the species that most closely matches
our linguistic prowess, you have to travel to a far more distant
relativeto a family of birds known as the songbirds. ~4,000 species
all over the world, in which the vocal organ is developed to
produce a diverse and elaborate bird song They learn songs by
imitating their elders. Songs are passed down from one generation
to the next. Also best equipped to learn songs in their youth Have
to practice to develop their ability. Improvise and string together
riffs into new songs Over generations modified songs turn into new
dialects. Hard-wired with speech-centers in brain for language
processing. Slide 7 Language and Songbirds Slide 8 Learn Language
from Birds Methods: By measuring how the songbirds response changes
with a new song, you can find out whether the bird can
differentiate between the songs. Teach grammar to the songbirds.
The birds were not surprised to hear the new grammatical sentences,
whereas the ungrammatical sentences would ruffle their feathers, so
to speak. Models Behavior Neuroscience Genetics Slide 9 Models of
the songs How human brains uniquely recombine a finite set of
sounds to generate infinite meaning (Hauser et al., 2002). Another
component of language, vocal learning, is also rare but not unique
to humans. Human speech and birdsong are the best characterized
exemplars of vocal learning, and the experimentally tractable
songbird has provided molecular and physiological insights. In
contrast, transgenically tractable rodents are not thought to learn
their vocalizations; however, the recent discovery that male mice
produce ultrasonic sounds that are song like (Holy and Guo, 2005)
reopens the question of whether such songs are learned. Disease
models: The discovery that mutations in the human gene encoding
forkhead box P2 (FOXP2), a transcription factor, result in speech
and language deficits (Lai et al., 2001; MacDermot et al., 2005)
Complexity of language and the variety of speech and language
disorders (which affect up to 1 in 20 children) Slide 10 Anatomy of
the songs avian syrinx 1 last free cartilaginous tracheal ring 2
Tympanum 3 first group of syringeal rings 4 Pessulus 5 Membrana
tympaniformis lateralis 6 Membrana tympaniformis medialis 7 second
group of syringeal rings 8 main bronchus 9 bronchial cartilage
Slide 11 Neuroscience of the songs Angular Gyrus Supramarginal
Gyrus Wernicke's Area: Language comprehension Broca's Area:
Language expression Primary Auditory Cortex Anterior forebrain
pathway (vocal learning) Posterior descending pathway (vocal
production) Slide 12 Neuroscience of Songs The acquisition and
learning of bird song involves a group of distinct brain areas that
are aligned in two connecting pathways: Anterior forebrain pathway
(vocal learning): composed of Area X, which is a homologue to
mammalian basal ganglia; the lateral part of the magnocellular
nucleus of anterior neostriatum (LMAN), also considered a part of
the avian basal ganglia; and the dorso-lateral division of the
medial thalamus (DLM). Posterior descending pathway (vocal
production): composed of HVC (proper name, although sometimes
referred to as the high vocal center); the robust nucleus of the
arcopallium (RA); and the tracheosyringeal part of the hypoglossal
nucleus (nXIIts). Slide 13 Bird song development timeline Slide 14
Slide 15 Hypothetical distributions of two behavioral phenotypes
Vocal learning: learn to produce elaborate patterns of structurally
organized vocalizations Sensory (auditory) sequence learning: the
ability to remember the detail of what is heard and the order in
which it was communicated Slide 16 Slide 17 Genetics of Songs Slide
18 Slide 19 Model system: The first bird genome: Chicken. The
second bird genome: Zebra finch The zebra finch is a tiny
Australian songbird. Only the males sing, and they learn a
particular song by listening to their fathers. As in all songbirds,
there is a discrete area of the forebrain called the "song control
center". During learning, nuclei in the song control center change
in size and organization, and during adulthood, the act of singing
alters the expression of genes. Slide 20 Genetics of Songs
Comparison: 1.The genomes of the two birds, genes that are most
likely to be important in singing and learning to sing could be
found. 2.The complimentary DNA from a juvenille songbird (learning
to sing) and an adult one (able to sing). Slide 21 Genetics of
Songs Comparison: 1.The genomes of the two birds, genes that are
most likely to be important in singing and learning to sing could
be found. 2.The complimentary DNA from a juvenille songbird
(learning to sing) and an adult one (able to sing). Slide 22
Genetics of Songs Comparison: 1.The genomes of the two birds, genes
that are most likely to be important in singing and learning to
sing could be found. 2.The complimentary DNA from a juvenille
songbird (learning to sing) and an adult one (able to sing). Slide
23 Genetics of Songs Comparison: 1.The genomes of the two birds,
genes that are most likely to be important in singing and learning
to sing could be found. 2.The complimentary DNA from a juvenille
songbird (learning to sing) and an adult one (able to sing).
Singing changes expression for over 800 genes in the song control
center RNAs in the finch's auditory centers also respond in
different ways as the bird learns a song. Many of the RNA
transcripts (40%) are non-coding, and of the RNAs that are
suppressed in response to song, the majority are non-coding. Also
activate small ncRNAs called microRNAs. A potential site of action
for the microRNAs aligns to an area in a human gene, NR4A3, that
encodes a transcription factor protein. Learning to sing is crucial
for the finch. It is likely that the genes involved, which include
genes that encode neuronal ion channels. Another possible channel
of evolution is gene duplications. For example the genes PHF7 and
PAK3 have been duplicated and many variants are present in the
finch's brain. Slide 24 Genetics of Songs Genetic mapping in an
unusual multigenerational family exhibiting a monogenic
communication disorder (Fisher et al., 1998) provided the first
link between FOXP2 and language (Lai et al., 2001). Affected
members of the KE family carry a heterozygous point mutation,
yielding an amino acid substitution (R553H) in the DNA-binding
domain of the FOXP2 protein. This tiny change correlates with a
multifaceted phenotype (Marcus and Fisher, 2003; Vargha-Khadem et
al., 2005) that includes profound deficits in learning and
production of complex sequences of mouth movements, impairing
speech (verbal dyspraxia), as well as wide-ranging problems with
language, extending beyond expressive domains (Watkins et al.,
2002a). 1.FOXP2-associated human disorder 2.Human neuron-like cells
to identify other elements in FOXP2-related pathways 3.Foxp2 mutant
mouse lines to study ultrasonic mouse songs 4.Songbirds: dynamic
regulation of FoxP2 during singing
