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Molecular Biology C SSheng Zhao ( 赵晟 ), Biochemistry and Molecular Department of Medical school in Southeast University CCouse QQ Club: 112342994 (

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Presentation on theme: "Molecular Biology C SSheng Zhao ( 赵晟 ), Biochemistry and Molecular Department of Medical school in Southeast University CCouse QQ Club: 112342994 ("— Presentation transcript:

1 Molecular Biology C SSheng Zhao ( 赵晟 ), Biochemistry and Molecular Department of Medical school in Southeast University CCouse QQ Club: ( 分子生物学 C ) WWeb: E or QQQ /MSN/Skype/gChat: MMobile: or Conception, theory, research, and application ——Logic and LIY (Learn It Yourself)

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)

3 How a song can change a genome

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.

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.

6 Why Songbirds ‘Uniquely human’? If you’re looking for the species that most closely matches our linguistic prowess, you have to travel to a far more distant relative——to 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.

7 Language and Songbirds

8 Learn Language from Birds Methods: By measuring how the songbird’s 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

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)

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

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)

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).

13 Bird song development timeline

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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

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17 Genetics of Songs

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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.

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).

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).

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).

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.

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


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